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Autophagy engaging and non-engaging hematopoietic stem cells

ABSTRACT: Autophagy engaging and non-engaging hematopoietic stem cells

PROVIDER: PRJNA958188 | ENA |

REPOSITORIES: ENA

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yHSC AThi oHSC ATlo oHSC Bulk RNA-seq - Understanding transcriptional changes between autophagy engaging and non-engaging hematopoietic stem cells during mouse aging.

Project description:We sought to understand the transcriptional profile of autophagy engaging vs non-engaging old hematopoietic stem cells (HSC) referenced against young HSCs. Bulk RNA-seq analyses indicated a large transcriptional divergence between the two oHSC subsets, with pathway analyses of differentially expressed genes (DEG) demonstrating enrichment in inflammatory signaling in AThi oHSCs and in oxidative metabolism signaling in ATlo oHSCs. Ingenuity Pathway Analysis (IPA) inferred that several inflammation-coupled pro-autophagy regulators including p53, Bnip3l, Nupr1, and Nlrp3[22,23], in addition to quiescence enforcing checkpoints FoxO3a, Rb1 and Cdkn1a, were activated in AThi oHSCs.

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Chaperone-mediated autophagy sustains hematopoietic stem cell function

Project description:Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production1, 2. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division3-8. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a role for chaperone-mediated autophagy (CMA)9, a selective form of lysosomal protein degradation, in sustaining adult HSC function. CMA is required for stem cell protein quality control and upregulation of fatty acid metabolism upon HSC activation. We identify that CMA activity decreases with age in HSC and show that genetic or pharmacological activation of CMA can restore functionality of old HSC. Together, our findings provide mechanistic insights into a new role for CMA in sustaining quality control, appropriate energetics and overall long-term hematopoietic stem cell function. Our work supports that CMA may be a promising therapeutic target to enhance hematopoietic stem cell function in conditions such as aging or stem cell transplantation.

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Autophagy engaging and non-engaging hematopoietic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-05-15 | GSE229137 | GEO

AThi oHSC ATlo oHSC WES - Identifying clonal differences or differences in mutation burden between autophagy engaging and non-engaging hematopoietic stem cells during mouse aging.

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