FOS Guards Quiescence and Potency in Human Hematopoietic Stem Cells [scRNA-seq]

Quiescence and limited dividing are critical in preserving potency of hematopoietic stem/progenitor cell (HSPCs) during lifetime, but little is known about how this process is regulated. Here, we show that the mobilized human HSPCs in peripheral blood (PB) are predominantly in a quiescent state, but rapidly exit quiescence and reduce repopulating potency in short-term culture. Through single cell RNA-seq, we identified a panel of regulators highly associated with HSC quiescence exit and cell-cycle entry. These regulators involve different biological processes such as cell-cycle, signaling pathways, metabolisms, etc. Among them, the oncogene, FOS restrains cell-cycle entry and supports repopulating potency in human HSCs through directly binding and regulating genes both for HSC quiescence and potency. Our findings uncover the regulatory program underlying quiescence exit and highlight the critical role of FOS to guard the quiescence and potency in human HSPCs. We compared the transcriptome of the eGFP+ and FOS/eGFP- hematopoietic stem cells by RNA-Seq