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| Status |
Public on Mar 03, 2017 |
| Title |
Autophagy maintains metabolism and functional activity of a subset of aged hematopoietic stem cells [ERRBS] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Autophagy is critical for protecting HSCs from metabolic stress. Here, we used a genetic approach to inactivate autophagy in adult HSCs by deleting the Atg12 gene. We show that loss of autophagy causes accumulation of mitochondria and an oxidative phosphorylation (OXPHOS)-activated metabolic state, which drives accelerated myeloid differentiation likely through epigenetic deregulations rather than transcriptional changes, and impairs HSC self-renewal activity and regenerative potential.
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| Overall design |
Quiescent HSCs HSCs (Lin-/c-Kit+/Sca-1+/Flk2-/CD150+/CD48-) were isolated from BL6 WT mice and activated HSCs were cultured 21 hours in cytokine+ media as described. DNA was extracted from -5 mice per group, and ERRBS was conducted as described in the methods. For cultured HSCs, HSCs were grown in StemPro34 medium (Invitrogen) supplemented with penicillin (50 U/ml)/streptomycin (50 μg/ml) and L-glutamine (2 mM), and with or without the following cytokines (±cyt): SCF (25 ng/ml), Flt3L (25 ng/ml), IL-11 (25 ng/ml), IL-3 (10 ng/ml), GM-CSF (10 ng/ml), Epo (4 U/ml) and Tpo (25 ng/ml) (Peprotech).
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| Contributor(s) |
Ho TT, Warr MR, Adelman ER, Verovskaya EV, Lansinger OM, Flach J, Figueroa ME, Passegué E |
| Citation(s) |
28241143 |
| Submission date |
Oct 31, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Emmanuelle Passegue |
| E-mail(s) |
passeguee@stemcell.ucsf.edu
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| Phone |
415-476-2426
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| Organization name |
The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco
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| Department |
Department of Medicine, Hem/Onc Division
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| Street address |
35 Medical Center Way, RMB-1017, Box 0667
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE81721 |
Autophagy maintains metabolism and functional activity of a subset of aged hematopoietic stem cells |
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| Relations |
| BioProject |
PRJNA351841 |
| SRA |
SRP092337 |
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