Live-animal imaging of native haematopoietic stem and progenitor cells
The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions 1 , 2 . It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achiev...
Gespeichert in:
Veröffentlicht in: | Nature (London) 2020-02, Vol.578 (7794), p.278-283 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 283 |
---|---|
container_issue | 7794 |
container_start_page | 278 |
container_title | Nature (London) |
container_volume | 578 |
creator | Christodoulou, Constantina Spencer, Joel A. Yeh, Shu-Chi A. Turcotte, Raphaël Kokkaliaris, Konstantinos D. Panero, Riccardo Ramos, Azucena Guo, Guoji Seyedhassantehrani, Negar Esipova, Tatiana V. Vinogradov, Sergei A. Rudzinskas, Sarah Zhang, Yi Perkins, Archibald S. Orkin, Stuart H. Calogero, Raffaele A. Schroeder, Timm Lin, Charles P. Camargo, Fernando D. |
description | The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions
1
,
2
. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow
3
–
5
. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.
A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow. |
doi_str_mv | 10.1038/s41586-020-1971-z |
format | Article |
fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2352050175</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A660675775</galeid><sourcerecordid>A660675775</sourcerecordid><originalsourceid>FETCH-LOGICAL-c573t-75e1cd3f50162a8d01ed98a45c159a3b73334ad8dfa72caf2bc93e1d461b6f563</originalsourceid><addsrcrecordid>eNp1kc1OJCEUhclEM7Y6D-DGVHTjBr1A8VNLY9SZpBM3uiY0RdVgqqCFahN9emnbn4kZN7C43z058CF0QOCUAFNnuSZcCQwUMGkkwc8_0IzUUuBaKLmFZgBUYVBM7KDdnO8BgBNZ_0Q7jALlwNgMXc39o8Mm-NEMVTl6H_oqdlUwUxlUf40bzRSX0bvJ2ypPbqxMaKtlir0Lfoqpsm4Y8j7a7syQ3a-3ew_dXV3eXvzG85vrPxfnc2y5ZBOW3BHbso4DEdSoFohrG2VqbglvDFtIxlhtWtV2RlJrOrqwDXOkrQVZiI4LtodONrmlwMPK5UmPPq8bmODiKmvKOIWSLnlBj7-g93GVQmlXKEEboJSpT6o3g9M-dHFKxq5D9bkQICSXr1lH_6Hs0j_ofyGygWyKOSfX6WUqP5qeNAG99qU3vnTxpde-9HPZOXwruVqMrv3YeBdUALoBchmF3qXPV3yf-gJaKJ3F</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2362902238</pqid></control><display><type>article</type><title>Live-animal imaging of native haematopoietic stem and progenitor cells</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><creator>Christodoulou, Constantina ; Spencer, Joel A. ; Yeh, Shu-Chi A. ; Turcotte, Raphaël ; Kokkaliaris, Konstantinos D. ; Panero, Riccardo ; Ramos, Azucena ; Guo, Guoji ; Seyedhassantehrani, Negar ; Esipova, Tatiana V. ; Vinogradov, Sergei A. ; Rudzinskas, Sarah ; Zhang, Yi ; Perkins, Archibald S. ; Orkin, Stuart H. ; Calogero, Raffaele A. ; Schroeder, Timm ; Lin, Charles P. ; Camargo, Fernando D.</creator><creatorcontrib>Christodoulou, Constantina ; Spencer, Joel A. ; Yeh, Shu-Chi A. ; Turcotte, Raphaël ; Kokkaliaris, Konstantinos D. ; Panero, Riccardo ; Ramos, Azucena ; Guo, Guoji ; Seyedhassantehrani, Negar ; Esipova, Tatiana V. ; Vinogradov, Sergei A. ; Rudzinskas, Sarah ; Zhang, Yi ; Perkins, Archibald S. ; Orkin, Stuart H. ; Calogero, Raffaele A. ; Schroeder, Timm ; Lin, Charles P. ; Camargo, Fernando D.</creatorcontrib><description>The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions
1
,
2
. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow
3
–
5
. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.
A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/s41586-020-1971-z</identifier><identifier>PMID: 32025033</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/100 ; 13/31 ; 14/19 ; 14/69 ; 38 ; 38/62 ; 38/91 ; 631/1647/245/2186 ; 631/532/1542 ; 64/60 ; Analysis ; Animals ; Blood vessels ; Bone imaging ; Bone marrow ; Bone Remodeling ; Bone turnover ; Cell cycle ; Cell Movement ; Cell Proliferation ; Cell Survival ; Domains ; Female ; fms-Like Tyrosine Kinase 3 - genetics ; fms-Like Tyrosine Kinase 3 - metabolism ; Genes, Reporter ; Hematopoietic stem cells ; Hematopoietic Stem Cells - metabolism ; Hemopoiesis ; Heterogeneity ; Humanities and Social Sciences ; Hypoxia ; Hypoxia - metabolism ; Imaging ; Imaging systems ; Labeling ; Localization ; Male ; MDS1 and EVI1 Complex Locus Protein - genetics ; MDS1 and EVI1 Complex Locus Protein - metabolism ; Methods ; Mice ; Molecular Imaging ; multidisciplinary ; Oxygen - metabolism ; Population ; Progenitor cells ; Science ; Science (multidisciplinary) ; Skull - cytology ; Stem cell transplantation ; Stem cells ; Transplantation ; Transplants & implants ; Visualization</subject><ispartof>Nature (London), 2020-02, Vol.578 (7794), p.278-283</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 13, 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-75e1cd3f50162a8d01ed98a45c159a3b73334ad8dfa72caf2bc93e1d461b6f563</citedby><cites>FETCH-LOGICAL-c573t-75e1cd3f50162a8d01ed98a45c159a3b73334ad8dfa72caf2bc93e1d461b6f563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41586-020-1971-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41586-020-1971-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32025033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Christodoulou, Constantina</creatorcontrib><creatorcontrib>Spencer, Joel A.</creatorcontrib><creatorcontrib>Yeh, Shu-Chi A.</creatorcontrib><creatorcontrib>Turcotte, Raphaël</creatorcontrib><creatorcontrib>Kokkaliaris, Konstantinos D.</creatorcontrib><creatorcontrib>Panero, Riccardo</creatorcontrib><creatorcontrib>Ramos, Azucena</creatorcontrib><creatorcontrib>Guo, Guoji</creatorcontrib><creatorcontrib>Seyedhassantehrani, Negar</creatorcontrib><creatorcontrib>Esipova, Tatiana V.</creatorcontrib><creatorcontrib>Vinogradov, Sergei A.</creatorcontrib><creatorcontrib>Rudzinskas, Sarah</creatorcontrib><creatorcontrib>Zhang, Yi</creatorcontrib><creatorcontrib>Perkins, Archibald S.</creatorcontrib><creatorcontrib>Orkin, Stuart H.</creatorcontrib><creatorcontrib>Calogero, Raffaele A.</creatorcontrib><creatorcontrib>Schroeder, Timm</creatorcontrib><creatorcontrib>Lin, Charles P.</creatorcontrib><creatorcontrib>Camargo, Fernando D.</creatorcontrib><title>Live-animal imaging of native haematopoietic stem and progenitor cells</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions
1
,
2
. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow
3
–
5
. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.
A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.</description><subject>13</subject><subject>13/100</subject><subject>13/31</subject><subject>14/19</subject><subject>14/69</subject><subject>38</subject><subject>38/62</subject><subject>38/91</subject><subject>631/1647/245/2186</subject><subject>631/532/1542</subject><subject>64/60</subject><subject>Analysis</subject><subject>Animals</subject><subject>Blood vessels</subject><subject>Bone imaging</subject><subject>Bone marrow</subject><subject>Bone Remodeling</subject><subject>Bone turnover</subject><subject>Cell cycle</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Domains</subject><subject>Female</subject><subject>fms-Like Tyrosine Kinase 3 - genetics</subject><subject>fms-Like Tyrosine Kinase 3 - metabolism</subject><subject>Genes, Reporter</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Hemopoiesis</subject><subject>Heterogeneity</subject><subject>Humanities and Social Sciences</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>Imaging</subject><subject>Imaging systems</subject><subject>Labeling</subject><subject>Localization</subject><subject>Male</subject><subject>MDS1 and EVI1 Complex Locus Protein - genetics</subject><subject>MDS1 and EVI1 Complex Locus Protein - metabolism</subject><subject>Methods</subject><subject>Mice</subject><subject>Molecular Imaging</subject><subject>multidisciplinary</subject><subject>Oxygen - metabolism</subject><subject>Population</subject><subject>Progenitor cells</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Skull - cytology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Visualization</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kc1OJCEUhclEM7Y6D-DGVHTjBr1A8VNLY9SZpBM3uiY0RdVgqqCFahN9emnbn4kZN7C43z058CF0QOCUAFNnuSZcCQwUMGkkwc8_0IzUUuBaKLmFZgBUYVBM7KDdnO8BgBNZ_0Q7jALlwNgMXc39o8Mm-NEMVTl6H_oqdlUwUxlUf40bzRSX0bvJ2ypPbqxMaKtlir0Lfoqpsm4Y8j7a7syQ3a-3ew_dXV3eXvzG85vrPxfnc2y5ZBOW3BHbso4DEdSoFohrG2VqbglvDFtIxlhtWtV2RlJrOrqwDXOkrQVZiI4LtodONrmlwMPK5UmPPq8bmODiKmvKOIWSLnlBj7-g93GVQmlXKEEboJSpT6o3g9M-dHFKxq5D9bkQICSXr1lH_6Hs0j_ofyGygWyKOSfX6WUqP5qeNAG99qU3vnTxpde-9HPZOXwruVqMrv3YeBdUALoBchmF3qXPV3yf-gJaKJ3F</recordid><startdate>20200213</startdate><enddate>20200213</enddate><creator>Christodoulou, Constantina</creator><creator>Spencer, Joel A.</creator><creator>Yeh, Shu-Chi A.</creator><creator>Turcotte, Raphaël</creator><creator>Kokkaliaris, Konstantinos D.</creator><creator>Panero, Riccardo</creator><creator>Ramos, Azucena</creator><creator>Guo, Guoji</creator><creator>Seyedhassantehrani, Negar</creator><creator>Esipova, Tatiana V.</creator><creator>Vinogradov, Sergei A.</creator><creator>Rudzinskas, Sarah</creator><creator>Zhang, Yi</creator><creator>Perkins, Archibald S.</creator><creator>Orkin, Stuart H.</creator><creator>Calogero, Raffaele A.</creator><creator>Schroeder, Timm</creator><creator>Lin, Charles P.</creator><creator>Camargo, Fernando D.</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>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>AEUYN</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>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</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></search><sort><creationdate>20200213</creationdate><title>Live-animal imaging of native haematopoietic stem and progenitor cells</title><author>Christodoulou, Constantina ; Spencer, Joel A. ; Yeh, Shu-Chi A. ; Turcotte, Raphaël ; Kokkaliaris, Konstantinos D. ; Panero, Riccardo ; Ramos, Azucena ; Guo, Guoji ; Seyedhassantehrani, Negar ; Esipova, Tatiana V. ; Vinogradov, Sergei A. ; Rudzinskas, Sarah ; Zhang, Yi ; Perkins, Archibald S. ; Orkin, Stuart H. ; Calogero, Raffaele A. ; Schroeder, Timm ; Lin, Charles P. ; Camargo, Fernando D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-75e1cd3f50162a8d01ed98a45c159a3b73334ad8dfa72caf2bc93e1d461b6f563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13</topic><topic>13/100</topic><topic>13/31</topic><topic>14/19</topic><topic>14/69</topic><topic>38</topic><topic>38/62</topic><topic>38/91</topic><topic>631/1647/245/2186</topic><topic>631/532/1542</topic><topic>64/60</topic><topic>Analysis</topic><topic>Animals</topic><topic>Blood vessels</topic><topic>Bone imaging</topic><topic>Bone marrow</topic><topic>Bone Remodeling</topic><topic>Bone turnover</topic><topic>Cell cycle</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Domains</topic><topic>Female</topic><topic>fms-Like Tyrosine Kinase 3 - genetics</topic><topic>fms-Like Tyrosine Kinase 3 - metabolism</topic><topic>Genes, Reporter</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Hemopoiesis</topic><topic>Heterogeneity</topic><topic>Humanities and Social Sciences</topic><topic>Hypoxia</topic><topic>Hypoxia - metabolism</topic><topic>Imaging</topic><topic>Imaging systems</topic><topic>Labeling</topic><topic>Localization</topic><topic>Male</topic><topic>MDS1 and EVI1 Complex Locus Protein - genetics</topic><topic>MDS1 and EVI1 Complex Locus Protein - metabolism</topic><topic>Methods</topic><topic>Mice</topic><topic>Molecular Imaging</topic><topic>multidisciplinary</topic><topic>Oxygen - metabolism</topic><topic>Population</topic><topic>Progenitor cells</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Skull - cytology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><topic>Visualization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Christodoulou, Constantina</creatorcontrib><creatorcontrib>Spencer, Joel A.</creatorcontrib><creatorcontrib>Yeh, Shu-Chi A.</creatorcontrib><creatorcontrib>Turcotte, Raphaël</creatorcontrib><creatorcontrib>Kokkaliaris, Konstantinos D.</creatorcontrib><creatorcontrib>Panero, Riccardo</creatorcontrib><creatorcontrib>Ramos, Azucena</creatorcontrib><creatorcontrib>Guo, Guoji</creatorcontrib><creatorcontrib>Seyedhassantehrani, Negar</creatorcontrib><creatorcontrib>Esipova, Tatiana V.</creatorcontrib><creatorcontrib>Vinogradov, Sergei A.</creatorcontrib><creatorcontrib>Rudzinskas, Sarah</creatorcontrib><creatorcontrib>Zhang, Yi</creatorcontrib><creatorcontrib>Perkins, Archibald S.</creatorcontrib><creatorcontrib>Orkin, Stuart H.</creatorcontrib><creatorcontrib>Calogero, Raffaele A.</creatorcontrib><creatorcontrib>Schroeder, Timm</creatorcontrib><creatorcontrib>Lin, Charles P.</creatorcontrib><creatorcontrib>Camargo, Fernando D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & 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>Health & Medical Collection</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</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 & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & 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 & 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 Korea</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 & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>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 & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</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>Christodoulou, Constantina</au><au>Spencer, Joel A.</au><au>Yeh, Shu-Chi A.</au><au>Turcotte, Raphaël</au><au>Kokkaliaris, Konstantinos D.</au><au>Panero, Riccardo</au><au>Ramos, Azucena</au><au>Guo, Guoji</au><au>Seyedhassantehrani, Negar</au><au>Esipova, Tatiana V.</au><au>Vinogradov, Sergei A.</au><au>Rudzinskas, Sarah</au><au>Zhang, Yi</au><au>Perkins, Archibald S.</au><au>Orkin, Stuart H.</au><au>Calogero, Raffaele A.</au><au>Schroeder, Timm</au><au>Lin, Charles P.</au><au>Camargo, Fernando D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Live-animal imaging of native haematopoietic stem and progenitor cells</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2020-02-13</date><risdate>2020</risdate><volume>578</volume><issue>7794</issue><spage>278</spage><epage>283</epage><pages>278-283</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions
1
,
2
. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow
3
–
5
. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.
A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32025033</pmid><doi>10.1038/s41586-020-1971-z</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0028-0836 |
ispartof | Nature (London), 2020-02, Vol.578 (7794), p.278-283 |
issn | 0028-0836 1476-4687 |
language | eng |
recordid | cdi_proquest_miscellaneous_2352050175 |
source | MEDLINE; SpringerLink Journals; Nature Journals Online |
subjects | 13 13/100 13/31 14/19 14/69 38 38/62 38/91 631/1647/245/2186 631/532/1542 64/60 Analysis Animals Blood vessels Bone imaging Bone marrow Bone Remodeling Bone turnover Cell cycle Cell Movement Cell Proliferation Cell Survival Domains Female fms-Like Tyrosine Kinase 3 - genetics fms-Like Tyrosine Kinase 3 - metabolism Genes, Reporter Hematopoietic stem cells Hematopoietic Stem Cells - metabolism Hemopoiesis Heterogeneity Humanities and Social Sciences Hypoxia Hypoxia - metabolism Imaging Imaging systems Labeling Localization Male MDS1 and EVI1 Complex Locus Protein - genetics MDS1 and EVI1 Complex Locus Protein - metabolism Methods Mice Molecular Imaging multidisciplinary Oxygen - metabolism Population Progenitor cells Science Science (multidisciplinary) Skull - cytology Stem cell transplantation Stem cells Transplantation Transplants & implants Visualization |
title | Live-animal imaging of native haematopoietic stem and progenitor cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T10%3A50%3A45IST&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=Live-animal%20imaging%20of%20native%20haematopoietic%20stem%20and%20progenitor%20cells&rft.jtitle=Nature%20(London)&rft.au=Christodoulou,%20Constantina&rft.date=2020-02-13&rft.volume=578&rft.issue=7794&rft.spage=278&rft.epage=283&rft.pages=278-283&rft.issn=0028-0836&rft.eissn=1476-4687&rft_id=info:doi/10.1038/s41586-020-1971-z&rft_dat=%3Cgale_proqu%3EA660675775%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=2362902238&rft_id=info:pmid/32025033&rft_galeid=A660675775&rfr_iscdi=true |