Extensive phylogenies of human development inferred from somatic mutations

Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing 1 , 2 . Here we reconstruct extensive phylogenies of normal tissues from three adult i...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature (London) 2021-09, Vol.597 (7876), p.387-392
Hauptverfasser: Coorens, Tim H. H., Moore, Luiza, Robinson, Philip S., Sanghvi, Rashesh, Christopher, Joseph, Hewinson, James, Przybilla, Moritz J., Lawson, Andrew R. J., Spencer Chapman, Michael, Cagan, Alex, Oliver, Thomas R. W., Neville, Matthew D. C., Hooks, Yvette, Noorani, Ayesha, Mitchell, Thomas J., Fitzgerald, Rebecca C., Campbell, Peter J., Martincorena, Iñigo, Rahbari, Raheleh, Stratton, Michael R.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 392
container_issue 7876
container_start_page 387
container_title Nature (London)
container_volume 597
creator Coorens, Tim H. H.
Moore, Luiza
Robinson, Philip S.
Sanghvi, Rashesh
Christopher, Joseph
Hewinson, James
Przybilla, Moritz J.
Lawson, Andrew R. J.
Spencer Chapman, Michael
Cagan, Alex
Oliver, Thomas R. W.
Neville, Matthew D. C.
Hooks, Yvette
Noorani, Ayesha
Mitchell, Thomas J.
Fitzgerald, Rebecca C.
Campbell, Peter J.
Martincorena, Iñigo
Rahbari, Raheleh
Stratton, Michael R.
description Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing 1 , 2 . Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals. Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.
doi_str_mv 10.1038/s41586-021-03790-y
format Article
fullrecord <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2564947649</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A675564061</galeid><sourcerecordid>A675564061</sourcerecordid><originalsourceid>FETCH-LOGICAL-c621t-a49941fa3f8153effdc3a541650f0f14cfc5bda68e9ec38a0883617f741819ec3</originalsourceid><addsrcrecordid>eNp90kFvFCEUB3BiNHZt_QIezMReNIYKA8Mwx82mak2jSVvjkVDmsZ1mBqbANN1vL-vW1jWr4UDC_N4_w-Mh9IqSI0qY_BA5raTApKSYsLohePUEzSivBeZC1k_RjJBSYiKZ2EMvYrwmhFS05s_RHuOcsUawGfpyfJfAxe4WivFq1fsluA5i4W1xNQ3aFS3cQu_HAVwqOmchBGgLG_xQRD_o1JlimFLevYsH6JnVfYSX9_s--v7x-GLxGZ9--3SymJ9iI0qasOZNw6nVzEpaMbC2NUxXnIqKWGIpN9ZUl60WEhowTGoi8wVobWtOJV0f7aO3m9wx-JsJYlJDFw30vXbgp6jKSvAmd4E3mR7-Ra_9FFz-u6xqzoUQRDyqpe5B5Vv6FLRZh6q5qKscRwTNCu9QuV8QdO8d2C4fb_k3O7wZuxv1JzragfJqYejMztR3WwXZJLhLSz3FqE7Oz7bt-3_b-cWPxddtXW60CT7GAFaNoRt0WClK1Hre1GbeVJ439Wve1CoXvb5v8HQ5QPtQ8nvAMmAbEPMnt4Tw-AL_if0JMzfcJA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2574466606</pqid></control><display><type>article</type><title>Extensive phylogenies of human development inferred from somatic mutations</title><source>MEDLINE</source><source>Springer Nature - Connect here FIRST to enable access</source><source>Alma/SFX Local Collection</source><creator>Coorens, Tim H. H. ; Moore, Luiza ; Robinson, Philip S. ; Sanghvi, Rashesh ; Christopher, Joseph ; Hewinson, James ; Przybilla, Moritz J. ; Lawson, Andrew R. J. ; Spencer Chapman, Michael ; Cagan, Alex ; Oliver, Thomas R. W. ; Neville, Matthew D. C. ; Hooks, Yvette ; Noorani, Ayesha ; Mitchell, Thomas J. ; Fitzgerald, Rebecca C. ; Campbell, Peter J. ; Martincorena, Iñigo ; Rahbari, Raheleh ; Stratton, Michael R.</creator><creatorcontrib>Coorens, Tim H. H. ; Moore, Luiza ; Robinson, Philip S. ; Sanghvi, Rashesh ; Christopher, Joseph ; Hewinson, James ; Przybilla, Moritz J. ; Lawson, Andrew R. J. ; Spencer Chapman, Michael ; Cagan, Alex ; Oliver, Thomas R. W. ; Neville, Matthew D. C. ; Hooks, Yvette ; Noorani, Ayesha ; Mitchell, Thomas J. ; Fitzgerald, Rebecca C. ; Campbell, Peter J. ; Martincorena, Iñigo ; Rahbari, Raheleh ; Stratton, Michael R.</creatorcontrib><description>Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing 1 , 2 . Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals. Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/s41586-021-03790-y</identifier><identifier>PMID: 34433963</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/23 ; 631/136/2086/1986 ; 631/208/135 ; 631/208/212/2306 ; Apoptosis ; Asymmetry ; Brain - metabolism ; Cell division ; Cell Lineage - genetics ; Chromosomes, Human, Y - genetics ; Clone Cells - metabolism ; Cloning ; Colon ; Crypts ; Embryo, Mammalian - cytology ; Embryo, Mammalian - metabolism ; Embryogenesis ; Embryonic Development - genetics ; Epithelium ; Gene sequencing ; Genetic aspects ; Genomes ; Genomics ; Germ cells ; Germ-Line Mutation - genetics ; Human growth ; Humanities and Social Sciences ; Humans ; Lasers ; Male ; Mosaicism ; multidisciplinary ; Mutation ; Mutation (Biology) ; Organ Specificity - genetics ; Pattern formation ; Phylogeny ; Physiological aspects ; Physiological research ; Polymorphism, Single Nucleotide - genetics ; Progenitor cells ; Science ; Science (multidisciplinary) ; Somatic cells ; Whole genome sequencing ; Zygotes</subject><ispartof>Nature (London), 2021-09, Vol.597 (7876), p.387-392</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 16, 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c621t-a49941fa3f8153effdc3a541650f0f14cfc5bda68e9ec38a0883617f741819ec3</citedby><cites>FETCH-LOGICAL-c621t-a49941fa3f8153effdc3a541650f0f14cfc5bda68e9ec38a0883617f741819ec3</cites><orcidid>0000-0002-5826-3554 ; 0000-0001-5315-516X ; 0000-0002-5320-8193 ; 0000-0001-6035-153X ; 0000-0003-0761-9503 ; 0000-0002-2059-0154 ; 0000-0002-7857-4771 ; 0000-0002-1839-7785 ; 0000-0002-7703-9216 ; 0000-0002-3921-0510 ; 0000-0003-1122-4416 ; 0000-0002-3434-3568 ; 0000-0001-5645-9492 ; 0000-0003-3592-1005 ; 0000-0003-4306-0102 ; 0000-0002-6237-7159 ; 0000-0001-5816-7936</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34433963$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Coorens, Tim H. H.</creatorcontrib><creatorcontrib>Moore, Luiza</creatorcontrib><creatorcontrib>Robinson, Philip S.</creatorcontrib><creatorcontrib>Sanghvi, Rashesh</creatorcontrib><creatorcontrib>Christopher, Joseph</creatorcontrib><creatorcontrib>Hewinson, James</creatorcontrib><creatorcontrib>Przybilla, Moritz J.</creatorcontrib><creatorcontrib>Lawson, Andrew R. J.</creatorcontrib><creatorcontrib>Spencer Chapman, Michael</creatorcontrib><creatorcontrib>Cagan, Alex</creatorcontrib><creatorcontrib>Oliver, Thomas R. W.</creatorcontrib><creatorcontrib>Neville, Matthew D. C.</creatorcontrib><creatorcontrib>Hooks, Yvette</creatorcontrib><creatorcontrib>Noorani, Ayesha</creatorcontrib><creatorcontrib>Mitchell, Thomas J.</creatorcontrib><creatorcontrib>Fitzgerald, Rebecca C.</creatorcontrib><creatorcontrib>Campbell, Peter J.</creatorcontrib><creatorcontrib>Martincorena, Iñigo</creatorcontrib><creatorcontrib>Rahbari, Raheleh</creatorcontrib><creatorcontrib>Stratton, Michael R.</creatorcontrib><title>Extensive phylogenies of human development inferred from somatic mutations</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing 1 , 2 . Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals. Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.</description><subject>45/23</subject><subject>631/136/2086/1986</subject><subject>631/208/135</subject><subject>631/208/212/2306</subject><subject>Apoptosis</subject><subject>Asymmetry</subject><subject>Brain - metabolism</subject><subject>Cell division</subject><subject>Cell Lineage - genetics</subject><subject>Chromosomes, Human, Y - genetics</subject><subject>Clone Cells - metabolism</subject><subject>Cloning</subject><subject>Colon</subject><subject>Crypts</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryogenesis</subject><subject>Embryonic Development - genetics</subject><subject>Epithelium</subject><subject>Gene sequencing</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Germ cells</subject><subject>Germ-Line Mutation - genetics</subject><subject>Human growth</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Lasers</subject><subject>Male</subject><subject>Mosaicism</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Mutation (Biology)</subject><subject>Organ Specificity - genetics</subject><subject>Pattern formation</subject><subject>Phylogeny</subject><subject>Physiological aspects</subject><subject>Physiological research</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Progenitor cells</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Somatic cells</subject><subject>Whole genome sequencing</subject><subject>Zygotes</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp90kFvFCEUB3BiNHZt_QIezMReNIYKA8Mwx82mak2jSVvjkVDmsZ1mBqbANN1vL-vW1jWr4UDC_N4_w-Mh9IqSI0qY_BA5raTApKSYsLohePUEzSivBeZC1k_RjJBSYiKZ2EMvYrwmhFS05s_RHuOcsUawGfpyfJfAxe4WivFq1fsluA5i4W1xNQ3aFS3cQu_HAVwqOmchBGgLG_xQRD_o1JlimFLevYsH6JnVfYSX9_s--v7x-GLxGZ9--3SymJ9iI0qasOZNw6nVzEpaMbC2NUxXnIqKWGIpN9ZUl60WEhowTGoi8wVobWtOJV0f7aO3m9wx-JsJYlJDFw30vXbgp6jKSvAmd4E3mR7-Ra_9FFz-u6xqzoUQRDyqpe5B5Vv6FLRZh6q5qKscRwTNCu9QuV8QdO8d2C4fb_k3O7wZuxv1JzragfJqYejMztR3WwXZJLhLSz3FqE7Oz7bt-3_b-cWPxddtXW60CT7GAFaNoRt0WClK1Hre1GbeVJ439Wve1CoXvb5v8HQ5QPtQ8nvAMmAbEPMnt4Tw-AL_if0JMzfcJA</recordid><startdate>20210916</startdate><enddate>20210916</enddate><creator>Coorens, Tim H. H.</creator><creator>Moore, Luiza</creator><creator>Robinson, Philip S.</creator><creator>Sanghvi, Rashesh</creator><creator>Christopher, Joseph</creator><creator>Hewinson, James</creator><creator>Przybilla, Moritz J.</creator><creator>Lawson, Andrew R. J.</creator><creator>Spencer Chapman, Michael</creator><creator>Cagan, Alex</creator><creator>Oliver, Thomas R. W.</creator><creator>Neville, Matthew D. C.</creator><creator>Hooks, Yvette</creator><creator>Noorani, Ayesha</creator><creator>Mitchell, Thomas J.</creator><creator>Fitzgerald, Rebecca C.</creator><creator>Campbell, Peter J.</creator><creator>Martincorena, Iñigo</creator><creator>Rahbari, Raheleh</creator><creator>Stratton, Michael R.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ATWCN</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5826-3554</orcidid><orcidid>https://orcid.org/0000-0001-5315-516X</orcidid><orcidid>https://orcid.org/0000-0002-5320-8193</orcidid><orcidid>https://orcid.org/0000-0001-6035-153X</orcidid><orcidid>https://orcid.org/0000-0003-0761-9503</orcidid><orcidid>https://orcid.org/0000-0002-2059-0154</orcidid><orcidid>https://orcid.org/0000-0002-7857-4771</orcidid><orcidid>https://orcid.org/0000-0002-1839-7785</orcidid><orcidid>https://orcid.org/0000-0002-7703-9216</orcidid><orcidid>https://orcid.org/0000-0002-3921-0510</orcidid><orcidid>https://orcid.org/0000-0003-1122-4416</orcidid><orcidid>https://orcid.org/0000-0002-3434-3568</orcidid><orcidid>https://orcid.org/0000-0001-5645-9492</orcidid><orcidid>https://orcid.org/0000-0003-3592-1005</orcidid><orcidid>https://orcid.org/0000-0003-4306-0102</orcidid><orcidid>https://orcid.org/0000-0002-6237-7159</orcidid><orcidid>https://orcid.org/0000-0001-5816-7936</orcidid></search><sort><creationdate>20210916</creationdate><title>Extensive phylogenies of human development inferred from somatic mutations</title><author>Coorens, Tim H. H. ; Moore, Luiza ; Robinson, Philip S. ; Sanghvi, Rashesh ; Christopher, Joseph ; Hewinson, James ; Przybilla, Moritz J. ; Lawson, Andrew R. J. ; Spencer Chapman, Michael ; Cagan, Alex ; Oliver, Thomas R. W. ; Neville, Matthew D. C. ; Hooks, Yvette ; Noorani, Ayesha ; Mitchell, Thomas J. ; Fitzgerald, Rebecca C. ; Campbell, Peter J. ; Martincorena, Iñigo ; Rahbari, Raheleh ; Stratton, Michael R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c621t-a49941fa3f8153effdc3a541650f0f14cfc5bda68e9ec38a0883617f741819ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>45/23</topic><topic>631/136/2086/1986</topic><topic>631/208/135</topic><topic>631/208/212/2306</topic><topic>Apoptosis</topic><topic>Asymmetry</topic><topic>Brain - metabolism</topic><topic>Cell division</topic><topic>Cell Lineage - genetics</topic><topic>Chromosomes, Human, Y - genetics</topic><topic>Clone Cells - metabolism</topic><topic>Cloning</topic><topic>Colon</topic><topic>Crypts</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryogenesis</topic><topic>Embryonic Development - genetics</topic><topic>Epithelium</topic><topic>Gene sequencing</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Germ cells</topic><topic>Germ-Line Mutation - genetics</topic><topic>Human growth</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Lasers</topic><topic>Male</topic><topic>Mosaicism</topic><topic>multidisciplinary</topic><topic>Mutation</topic><topic>Mutation (Biology)</topic><topic>Organ Specificity - genetics</topic><topic>Pattern formation</topic><topic>Phylogeny</topic><topic>Physiological aspects</topic><topic>Physiological research</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Progenitor cells</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Somatic cells</topic><topic>Whole genome sequencing</topic><topic>Zygotes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coorens, Tim H. H.</creatorcontrib><creatorcontrib>Moore, Luiza</creatorcontrib><creatorcontrib>Robinson, Philip S.</creatorcontrib><creatorcontrib>Sanghvi, Rashesh</creatorcontrib><creatorcontrib>Christopher, Joseph</creatorcontrib><creatorcontrib>Hewinson, James</creatorcontrib><creatorcontrib>Przybilla, Moritz J.</creatorcontrib><creatorcontrib>Lawson, Andrew R. J.</creatorcontrib><creatorcontrib>Spencer Chapman, Michael</creatorcontrib><creatorcontrib>Cagan, Alex</creatorcontrib><creatorcontrib>Oliver, Thomas R. W.</creatorcontrib><creatorcontrib>Neville, Matthew D. C.</creatorcontrib><creatorcontrib>Hooks, Yvette</creatorcontrib><creatorcontrib>Noorani, Ayesha</creatorcontrib><creatorcontrib>Mitchell, Thomas J.</creatorcontrib><creatorcontrib>Fitzgerald, Rebecca C.</creatorcontrib><creatorcontrib>Campbell, Peter J.</creatorcontrib><creatorcontrib>Martincorena, Iñigo</creatorcontrib><creatorcontrib>Rahbari, Raheleh</creatorcontrib><creatorcontrib>Stratton, Michael R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Middle School</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>ProQuest Nursing and Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric &amp; Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database (ProQuest)</collection><collection>ProQuest research library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest advanced technologies &amp; aerospace journals</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric &amp; Aquatic Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coorens, Tim H. H.</au><au>Moore, Luiza</au><au>Robinson, Philip S.</au><au>Sanghvi, Rashesh</au><au>Christopher, Joseph</au><au>Hewinson, James</au><au>Przybilla, Moritz J.</au><au>Lawson, Andrew R. J.</au><au>Spencer Chapman, Michael</au><au>Cagan, Alex</au><au>Oliver, Thomas R. W.</au><au>Neville, Matthew D. C.</au><au>Hooks, Yvette</au><au>Noorani, Ayesha</au><au>Mitchell, Thomas J.</au><au>Fitzgerald, Rebecca C.</au><au>Campbell, Peter J.</au><au>Martincorena, Iñigo</au><au>Rahbari, Raheleh</au><au>Stratton, Michael R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extensive phylogenies of human development inferred from somatic mutations</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2021-09-16</date><risdate>2021</risdate><volume>597</volume><issue>7876</issue><spage>387</spage><epage>392</epage><pages>387-392</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing 1 , 2 . Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals. Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34433963</pmid><doi>10.1038/s41586-021-03790-y</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-5826-3554</orcidid><orcidid>https://orcid.org/0000-0001-5315-516X</orcidid><orcidid>https://orcid.org/0000-0002-5320-8193</orcidid><orcidid>https://orcid.org/0000-0001-6035-153X</orcidid><orcidid>https://orcid.org/0000-0003-0761-9503</orcidid><orcidid>https://orcid.org/0000-0002-2059-0154</orcidid><orcidid>https://orcid.org/0000-0002-7857-4771</orcidid><orcidid>https://orcid.org/0000-0002-1839-7785</orcidid><orcidid>https://orcid.org/0000-0002-7703-9216</orcidid><orcidid>https://orcid.org/0000-0002-3921-0510</orcidid><orcidid>https://orcid.org/0000-0003-1122-4416</orcidid><orcidid>https://orcid.org/0000-0002-3434-3568</orcidid><orcidid>https://orcid.org/0000-0001-5645-9492</orcidid><orcidid>https://orcid.org/0000-0003-3592-1005</orcidid><orcidid>https://orcid.org/0000-0003-4306-0102</orcidid><orcidid>https://orcid.org/0000-0002-6237-7159</orcidid><orcidid>https://orcid.org/0000-0001-5816-7936</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0028-0836
ispartof Nature (London), 2021-09, Vol.597 (7876), p.387-392
issn 0028-0836
1476-4687
language eng
recordid cdi_proquest_miscellaneous_2564947649
source MEDLINE; Springer Nature - Connect here FIRST to enable access; Alma/SFX Local Collection
subjects 45/23
631/136/2086/1986
631/208/135
631/208/212/2306
Apoptosis
Asymmetry
Brain - metabolism
Cell division
Cell Lineage - genetics
Chromosomes, Human, Y - genetics
Clone Cells - metabolism
Cloning
Colon
Crypts
Embryo, Mammalian - cytology
Embryo, Mammalian - metabolism
Embryogenesis
Embryonic Development - genetics
Epithelium
Gene sequencing
Genetic aspects
Genomes
Genomics
Germ cells
Germ-Line Mutation - genetics
Human growth
Humanities and Social Sciences
Humans
Lasers
Male
Mosaicism
multidisciplinary
Mutation
Mutation (Biology)
Organ Specificity - genetics
Pattern formation
Phylogeny
Physiological aspects
Physiological research
Polymorphism, Single Nucleotide - genetics
Progenitor cells
Science
Science (multidisciplinary)
Somatic cells
Whole genome sequencing
Zygotes
title Extensive phylogenies of human development inferred from somatic mutations
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T06%3A45%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Extensive%20phylogenies%20of%20human%20development%20inferred%20from%20somatic%20mutations&rft.jtitle=Nature%20(London)&rft.au=Coorens,%20Tim%20H.%20H.&rft.date=2021-09-16&rft.volume=597&rft.issue=7876&rft.spage=387&rft.epage=392&rft.pages=387-392&rft.issn=0028-0836&rft.eissn=1476-4687&rft_id=info:doi/10.1038/s41586-021-03790-y&rft_dat=%3Cgale_proqu%3EA675564061%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2574466606&rft_id=info:pmid/34433963&rft_galeid=A675564061&rfr_iscdi=true