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Title: | Memory of Divisional History Directs the Continuous Process of Primitive Hematopoietic Lineage Commitment | Authors: | Bernitz, Jeffrey M Rapp, Katrina Daniel, Michael G. Shcherbinin, Dmitrii Yuan, Ye Gomes, Andreia Waghray, Avinash Brosh, Ran Lachmann, Alexander Ma'ayan, Avi Papatsenko, Dmitri Moore, Kateri A. |
Keywords: | cell heterogeneity; divisional history; epigenetics; hematopoietic stem cells; leukemia; memory; polycomb repressive complex | Issue Date: | 14-Apr-2020 | Publisher: | Cell Press | Project: | National Institutes of Health grant 2R01HL58739 New York Department of Health grant C32597GG National Institutes of Health grants T32HD075735 and F31HL131290 National Institutes of Health grants U54HL127624 and U24CA224260 |
Serial title, monograph or event: | Stem Cell Reports | Volume: | 14 | Issue: | 4 | Abstract: | Hematopoietic stem cells (HSCs) exist in a dormant state and progressively lose regenerative potency as they undergo successive divisions. Why this functional decline occurs and how this information is encoded is unclear. To better understand how this information is stored, we performed RNA sequencing on HSC populations differing only in their divisional history. Comparative analysis revealed that genes upregulated with divisions are enriched for lineage genes and regulated by cell-cycle-associated transcription factors, suggesting that proliferation itself drives lineage priming. Downregulated genes are, however, associated with an HSC signature and targeted by the Polycomb Repressive Complex 2 (PRC2). The PRC2 catalytic subunits Ezh1 and Ezh2 promote and suppress the HSC state, respectively, and successive divisions cause a switch from Ezh1 to Ezh2 dominance. We propose that cell divisions drive lineage priming and Ezh2 accumulation, which represses HSC signature genes to consolidate information on divisional history into memory. | URI: | https://hdl.handle.net/10316/106735 | ISSN: | 22136711 | DOI: | 10.1016/j.stemcr.2020.03.005 | Rights: | openAccess |
Appears in Collections: | IIIUC - Artigos em Revistas Internacionais |
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Memory of Divisional History Directs the Continuous Process of Primitive Hematopoietic Lineage Commitment.pdf | 3.99 MB | Adobe PDF | View/Open |
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