Microarray from both control and activated Hematopoietic stem cells

Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a central role for a selective type of autophagy (CMA) in sustaining adult HSC function both through to stem cell protein quality control and to timely stimulation of linoleic fatty acid metabolism upon HSC activation. We identify that reduced CMA in old HSC contributes to the loss of stem cell activity during aging and show that genetic or chemical activation of CMA can restore old HSC function. Together, our findings provide mechanistic insights into a new role for CMA in sustaining long-term HSC quality control, appropriate energetics and overall 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. We used microarrays to identify the most affected genes and pathways by CMA deficiency in both basal and activated conditions. Mice were injected with a single dose of 5FU to activate HSCs, mice were sacrificed and bone marrow were taken and sorted with hematopoietic stem and progenitor cell markers at day0 and day8 after the injection.