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| Status |
Public on Aug 07, 2015 |
| Title |
PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different H3K4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.
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| Overall design |
6 samples were hybridized GeneChip Human Gene 1.0 ST Arrays (Affymetrix)
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| Contributor(s) |
Varagnolo L, Lin Q, Obier N, Plass C, Dietl J, Zenke M, Claus R, Müller AM |
| Citation(s) |
26198814 |
| |
| Submission date |
Jun 13, 2014 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Martin Zenke |
| E-mail(s) |
[email protected]
|
| Phone |
+49-241-80 80760
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| Organization name |
Institute for Biomedical Engineering
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| Department |
Cell Biology
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| Street address |
Universitatsklinikum Aachen, RWTH
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| City |
Aachen |
| State/province |
NRW |
| ZIP/Postal code |
52074 |
| Country |
Germany |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA252679 |
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