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Mitochondrial reprogramming dictates hematopoietic stem cell fate in early development.

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Self-renewal and multilineage engraftment capacity of hematopoietic stem cells (HSCs) are key properties leveraged for their clinical use in bone marrow transplantation. Variations in the efficiency of long-term blood reconstitution are partly attributed to the functional heterogeneity in HSCs. In addition to differences in gene expression, the dynamic mitochondrial metabolic state also influences bone marrow (BM) HSC heterogeneity. We are interested in understanding whether metabolic variation is an outcome of the diverse milieus that HSCs reside in, or is an inherent property of the emergent HSCs. For this we study hematopoietic emergence during the endothelial to hematopoietic transition (EHT) in the aorta-gonad-mesonephros (AGM) region of mouse embryos. Our work will provide insights into the origin of functional heterogeneity in HSCs, which could be leveraged to enrich the desired HSC pool for efficient transplantation.

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