Hematopoietic stem cell heterogeneity and niche cell associations governing definitive hematopoiesis formation

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The primary goal of this project is to understand how hematopoietic stem cells (HSCs) are regulated during ontogeny by elucidating the various cell-intrinsic and cell-extrinsic factors (the BM niche) that may play a role. So far, our scRNA-seq data of neonatal P2 HSCs sampled from major hematopoietic organs has revealed three HSC groups (HSCin1, HSCin2 and HSCout) that are phenotypically and functionally (in vitro differentiation potential and in vivo reconstitution capacity) heterogenous. GO analysis of each group shows enrichment of distinct biological signatures and reinforces their specific role(s) during this temporal period. Our gene list was compared with zebrafish HSC RNA-seq data during definitive hematopoiesis formation and several genes that were significantly upregulated in both species that could potentially dictate “HSC maturation” were selected for further overexpression and downregulation studies. This is currently ongoing. We are simultaneously validating our scRNA-seq data with qPCR analysis, in vitro CFU and in vivo transplantation studies. Furthermore, we are currently devising other strategies for tracing these HSCs (barcoding) in vivo to directly investigate their contribution towards adult hematopoiesis.