SRP408664 PRJNA903209 GSE218359 CD34+ HSPC CITE-seq for day 0 and Day 1 and Day 4 under VPA The regenerative potential of human hematopoietic stem cells (HSCs) is well established by to their ability of life-long blood cell production and cure of a wide range of hematological diseases upon transplantation. This regenerative potential depends on HSC self-renewal and the coordinated adaptation to metabolic stress conditions. This is especially critical during ex vivo culture/manipulation of HSCs that is frequently accompanied with loss of self-renewal potential resulting in stem cell exhaustion. We have previously reported that CD34+ human hematopoietic stem and progenitor cells (HSPC) can be efficiently reprogrammed and expanded to phenotypic HSCs with long-term repopulation capacity in the presence of cytokines and valproic acid (VPA). Here, we present evidence that the SIRT1-SIRT3 axis maintains the mitochondrial activity below a critical threshold by coordinating and retaining a transcriptional and metabolic landscape of human HSCs with long-term self-renewal properties during ex vivo HSC reprogramming. Overall design: We performed CITE-sequencing to obtain measurement at the protein and transcriptome level in order to measure these data simultaneously in before (day 0) and after cytokines and valproic acid (VPA) (day 1 and day 4). GSE218359 pubmed 37001723