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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

101 Scopus Citations
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Author(s)

  • Vionnie W.C. Yu
  • Rushdia Z. Yusuf
  • Toshihiko Oki
  • Juwell Wu
  • Borja Saez
  • Colleen Cook
  • Ninib Baryawno
  • Michael J. Ziller
  • Eunjung Lee
  • Hongcang Gu
  • Alexander Meissner
  • Charles P. Lin
  • Peter V. Kharchenko
  • David T. Scadden

Detail(s)

Original languageEnglish
Pages (from-to)1310-1322.e17
Journal / PublicationCell
Volume167
Issue number5
Publication statusPublished - 17 Nov 2016
Externally publishedYes

Abstract

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.

Research Area(s)

  • ATAC-seq, clonal tracking, epigenetic memory, hematopoiesis, hematopoietic stem cell, lineage tracing, multi-fluorescent mouse model, RNA-seq, single cell, transplantation

Citation Format(s)

Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells. / Yu, Vionnie W.C.; Yusuf, Rushdia Z.; Oki, Toshihiko; Wu, Juwell; Saez, Borja; Wang, Xin; Cook, Colleen; Baryawno, Ninib; Ziller, Michael J.; Lee, Eunjung; Gu, Hongcang; Meissner, Alexander; Lin, Charles P.; Kharchenko, Peter V.; Scadden, David T.

In: Cell, Vol. 167, No. 5, 17.11.2016, p. 1310-1322.e17.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review