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| Status |
Public on Dec 04, 2018 |
| Title |
Aging alters the epigenetic asymmetry of HSC division [scATAC-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain homeostasis. With aging, the frequency of polar HSCs decreases. Cell polarity in HSCs is controlled by the activity of the small RhoGTPase Cdc42. Here we demonstrate, using a comprehensive set of paired daughter cell analyses that include single cell 3D-confocal imaging, single cell transplants, single cell RNA-seq as well as single cell ATAC-seq, that the outcome of HSC divisions is strongly linked to the polarity status before mitosis, which is in turn determined by the level of the activity Cdc42 in stem cells. Aged apolar HSCs undergo preferentially self-renewing symmetric divisions, resulting in daughter stem cells with reduced regenerative capacity and lymphoid potential, while young polar HSCs undergo preferentially asymmetric divisions. Mathematical modeling in combination with experimental data implies a mechanistic role of the asymmetric sorting of Cdc42 in determining the potential of daughter cells via epigenetic mechanisms. Therefore, molecules that control HSC polarity might serve as modulators of the mode of stem cell division regulating the potential of daughter cells.
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| Overall design |
Sorted single cells were cultured with and without treatment in the presence of cytokines until first cell division (40-44hrs). The daughter cells were manually separated, washed with PBS and collected for ATAC sequencing.
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| Contributor(s) |
Mulaw M |
| Citation(s) |
30235201 |
| |
| Submission date |
Jul 06, 2018 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Medhanie Assmelash Mulaw |
| E-mail(s) |
medhanie.mulaw@uni-ulm.de
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| Organization name |
University of Ulm
|
| Street address |
Albert-Einstein-Allee 11
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| City |
Ulm |
| ZIP/Postal code |
89081 |
| Country |
Germany |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (48)
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| This SubSeries is part of SuperSeries: |
| GSE116712 |
Aging alters the epigenetic asymmetry of HSC division |
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| Relations |
| BioProject |
PRJNA479966 |
| SRA |
SRP152506 |
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