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| Status |
Public on Nov 17, 2016 |
| Title |
Epigenetic Memory Underlies Cell Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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 are warranted.
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| Overall design |
LKS SLAM cells associated with different clonal clusters were separated using flow cytometry, and examined using RNA-seq, WGBS, ATAC-seq.
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| Contributor(s) |
Yu VW, Kharchenko PV, Scadden DT |
| Citation(s) |
27863245 |
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| Submission date |
Sep 30, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter Kharchenko |
| Organization name |
Harvard Medical School
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| Department |
DBMI
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| Lab |
Kharchenko
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| Street address |
10 Shattuck St.
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA345018 |
| SRA |
SRP090698 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE87527_RAW.tar |
1.1 Gb |
(http)(custom) |
TAR (of BED, TDF, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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