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

Yu, V. W. C., Yusuf, R. Z., Oki, T., Wu, J., Saez, B., Wang, X., et al. (2016). Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells. Cell, 167(5): e17, pp. 1310-1322. doi:10.1016/j.cell.2016.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-DF30-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-DF5C-5
Genre: Journal Article

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© 2016 Elsevier B.V.
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 Creators:
Yu , Vionnie W. C. , Author
Yusuf , Rushdia Z. , Author
Oki , Toshihiko , Author
Wu, Juwell, Author
Saez, Borja , Author
Wang, Xin, Author
Cook , Colleen, Author
Baryawno , Ninib , Author
Ziller , Michael J. , Author
Lee , Eunjung , Author
Gu, Hongcang, Author
Meissner, Alexander1, 2, Author              
Lin, Charles P. , Author
Kharchenko, Peter V. , Author
Scadden , David T. , Author
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA, ou_persistent22              

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Free keywords: ATAC-seq; RNA-seq; clonal tracking; epigenetic memory; hematopoiesis; hematopoietic stem cell; lineage tracing; multi-fluorescent mouse model; single cell; transplantation
 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.

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Language(s): eng - English
 Dates: 2016-11-17
 Publication Status: Published online
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.cell.2016
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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 167 (5) Sequence Number: e17 Start / End Page: 1310 - 1322 Identifier: ISSN: 0092-8674
CoNE: /journals/resource/954925463183