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The complex and tightly regulated process of human hematopoietic development culminates in the production of hematopoietic stem cells (HSCs), which subsequently undergo expansion in the fetal liver (FL). The establishment of a high-resolution molecular signature of FL-HSCs would provide insights into HSC biology with potential utility in the purification and expansion of engraftable HSCs ex vivo and the generation of HSCs from pluripotent cell sources. To profile HSCs at this developmental stage, we performed CITE-Seq, a technique that combines single cell RNA sequencing (scRNAseq) and cell surface marker interrogation using oligo-tagged antibodies. To connect expression profiles with functional engraftment, we have coupled this with transplantation assays in immunocompromised mice.

In these studies, three populations of human FL cells were used: CD34- cells, CD34+ cells and CD34+ cells further …