Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis
Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and rep...
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| Veröffentlicht in: | Nature genetics 2023-02, Vol.55 (2), p.333-345 |
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| creator | Zeller, Peter Yeung, Jake Viñas Gaza, Helena de Barbanson, Buys Anton Bhardwaj, Vivek Florescu, Maria van der Linden, Reinier van Oudenaarden, Alexander |
| description | Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages.
Sort-assisted single-cell chromatin immunocleavage (sortChIC) combines single-cell histone modification profiling with fluorescence-activated cell sorting (FACS), enabling the study of rare cell populations. H3K4me1/H3K4me3, H3K9me3 and H3K27me3 profiling of blood suggest a model of lineage-shared repressive and cell type-specific active chromatin. |
| doi_str_mv | 10.1038/s41588-022-01260-3 |
| format | Article |
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Sort-assisted single-cell chromatin immunocleavage (sortChIC) combines single-cell histone modification profiling with fluorescence-activated cell sorting (FACS), enabling the study of rare cell populations. H3K4me1/H3K4me3, H3K9me3 and H3K27me3 profiling of blood suggest a model of lineage-shared repressive and cell type-specific active chromatin.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/s41588-022-01260-3</identifier><identifier>PMID: 36539617</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/136/532 ; 631/1647/514/1948 ; 631/208/177 ; 631/337/176 ; Agriculture ; Animal Genetics and Genomics ; Animals ; Antibodies ; Biomedical and Life Sciences ; Biomedicine ; Blood ; Bone marrow ; Cancer Research ; Cell cycle ; Cell differentiation ; Cell Differentiation - genetics ; Cell Lineage - genetics ; Cells (biology) ; Chromatin ; Chromatin - genetics ; Differentiation ; Epigenesis, Genetic ; Euchromatin ; Gene expression ; Gene Function ; Genomes ; Hematopoiesis ; Hematopoiesis - genetics ; Hematopoietic stem cells ; Heterochromatin ; Heterochromatin - genetics ; Histones ; Human Genetics ; Mice ; Post-translation ; Progenitor cells ; technical-report ; Trajectory analysis ; Transcription factors</subject><ispartof>Nature genetics, 2023-02, Vol.55 (2), p.333-345</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>Copyright Nature Publishing Group Feb 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-c505a5037ac8d60dd4b52d9cb498aa8c2b8d909647240d6a2765739da898ef973</citedby><cites>FETCH-LOGICAL-c474t-c505a5037ac8d60dd4b52d9cb498aa8c2b8d909647240d6a2765739da898ef973</cites><orcidid>0000-0002-4898-2862 ; 0000-0003-1732-1559 ; 0000-0001-7437-8901 ; 0000-0002-5570-9338 ; 0000-0002-9442-3551</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41588-022-01260-3$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41588-022-01260-3$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36539617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zeller, Peter</creatorcontrib><creatorcontrib>Yeung, Jake</creatorcontrib><creatorcontrib>Viñas Gaza, Helena</creatorcontrib><creatorcontrib>de Barbanson, Buys Anton</creatorcontrib><creatorcontrib>Bhardwaj, Vivek</creatorcontrib><creatorcontrib>Florescu, Maria</creatorcontrib><creatorcontrib>van der Linden, Reinier</creatorcontrib><creatorcontrib>van Oudenaarden, Alexander</creatorcontrib><title>Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages.
Sort-assisted single-cell chromatin immunocleavage (sortChIC) combines single-cell histone modification profiling with fluorescence-activated cell sorting (FACS), enabling the study of rare cell populations. H3K4me1/H3K4me3, H3K9me3 and H3K27me3 profiling of blood suggest a model of lineage-shared repressive and cell type-specific active chromatin.</description><subject>631/136/532</subject><subject>631/1647/514/1948</subject><subject>631/208/177</subject><subject>631/337/176</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Cancer Research</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Lineage - genetics</subject><subject>Cells (biology)</subject><subject>Chromatin</subject><subject>Chromatin - genetics</subject><subject>Differentiation</subject><subject>Epigenesis, Genetic</subject><subject>Euchromatin</subject><subject>Gene expression</subject><subject>Gene Function</subject><subject>Genomes</subject><subject>Hematopoiesis</subject><subject>Hematopoiesis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeller, Peter</au><au>Yeung, Jake</au><au>Viñas Gaza, Helena</au><au>de Barbanson, Buys Anton</au><au>Bhardwaj, Vivek</au><au>Florescu, Maria</au><au>van der Linden, Reinier</au><au>van Oudenaarden, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>55</volume><issue>2</issue><spage>333</spage><epage>345</epage><pages>333-345</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages.
Sort-assisted single-cell chromatin immunocleavage (sortChIC) combines single-cell histone modification profiling with fluorescence-activated cell sorting (FACS), enabling the study of rare cell populations. H3K4me1/H3K4me3, H3K9me3 and H3K27me3 profiling of blood suggest a model of lineage-shared repressive and cell type-specific active chromatin.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>36539617</pmid><doi>10.1038/s41588-022-01260-3</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-4898-2862</orcidid><orcidid>https://orcid.org/0000-0003-1732-1559</orcidid><orcidid>https://orcid.org/0000-0001-7437-8901</orcidid><orcidid>https://orcid.org/0000-0002-5570-9338</orcidid><orcidid>https://orcid.org/0000-0002-9442-3551</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/136/532 631/1647/514/1948 631/208/177 631/337/176 Agriculture Animal Genetics and Genomics Animals Antibodies Biomedical and Life Sciences Biomedicine Blood Bone marrow Cancer Research Cell cycle Cell differentiation Cell Differentiation - genetics Cell Lineage - genetics Cells (biology) Chromatin Chromatin - genetics Differentiation Epigenesis, Genetic Euchromatin Gene expression Gene Function Genomes Hematopoiesis Hematopoiesis - genetics Hematopoietic stem cells Heterochromatin Heterochromatin - genetics Histones Human Genetics Mice Post-translation Progenitor cells technical-report Trajectory analysis Transcription factors |
| title | Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis |
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