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| Status |
Public on Sep 18, 2016 |
| Title |
Progressive chromatin condensation and H3K9 methylation regulate the differentiation of embryonic and hematopoietic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion between pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem and progenitor cells (HSPCs), and mature hematopoietic cells. Quantification of chromatin composition by high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSPCs, with a further reduction in euchromatin as HSPCs transition into mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9a resulted in delayed hematopoietic stem cell (HSC) differentiation. Our results demonstrate significant global rearrangements of chromatin structure during embryonic and adult stem cell differentiation, and that heterochromatin formation by H3K9 methylation is an important regulator of HSC differentiation.
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| Overall design |
Examination of gene expression profile of in vitro cultured mouse HSC with the G9a inhibitor UNC0638
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| Contributor(s) |
Forsberg C, Ugarte F, Krietsch J, Sousae R |
| Citation(s) |
26489895 |
| |
| Submission date |
Sep 18, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Camilla Forsberg |
| E-mail(s) |
cforsber@soe.ucsc.edu
|
| Organization name |
University of California Santa Cruz
|
| Department |
Biomolecular engineering
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| Street address |
1156 High st
|
| City |
Santa Cruz |
| State/province |
CA |
| ZIP/Postal code |
95064 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA296390 |
| SRA |
SRP063877 |
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