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

Cell | Nov 17, 2016

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 over time 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: 27863245 RIS Download

Mesh terms: Animals | Cell Lineage | Clone Cells | Epigenomics | Fluorescence | Hematopoiesis | Hematopoietic Stem Cells | Inflammation | Mice | Transcription, Genetic

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Associated grants

  • Agency: NIA NIH HHS, Id: K25 AG037596
  • Agency: NHLBI NIH HHS, Id: R01 HL131768
  • Agency: NCI NIH HHS, Id: U54 CA193461
  • Agency: NIDDK NIH HHS, Id: R24 DK103074

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