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Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells.

Cell | 2017

Stem cells determine homeostasis and repair of many tissues and are increasingly recognized as functionally heterogeneous. To define the extent of—and molecular basis for—heterogeneity, we overlaid functional, transcriptional, and epigenetic attributes of hematopoietic stem cells (HSCs) at a clonal level using endogenous fluorescent tagging. Endogenous HSC had clone-specific functional attributes in vivo. The intra-clonal behaviors were highly stereotypic, conserved under the stress of transplantation, inflammation, and genotoxic injury, and associated with distinctive transcriptional, DNA methylation, and chromatin accessibility patterns. Further, HSC function corresponded to epigenetic configuration but not always to transcriptional state. Therefore, hematopoiesis under homeostatic and stress conditions represents the integrated action of highly heterogeneous clones of HSC with epigenetically scripted behaviors. This high degree of epigenetically driven cell autonomy among HSCs implies that refinement of the concepts of stem cell plasticity and of the stem cell niche is warranted.

Pubmed ID: 28235203 RIS Download

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: K25 AG037596
  • Agency: NHLBI NIH HHS, United States
    Id: R21 HL126070
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL131477
  • Agency: NIDDK NIH HHS, United States
    Id: R24 DK103074
  • Agency: NCI NIH HHS, United States
    Id: U54 CA193461

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