Cell-intrinsic factors governing quiescence vis-a-vis activation of adult hematopoietic stem cells

Hematopoiesis is a highly complex process, regulated by both intrinsic and extrinsic factors. Often, these two regulatory arms work in tandem to maintain the steady-state condition of hematopoiesis. However, at times, certain intrinsic attributes of hematopoietic stem cells (HSCs) override the external stimuli and dominate the outcome. These could be genetic events like mutations or environmentally induced epigenetic or transcriptomic changes. Since leukemic stem cells (LSCs) share molecular pathways that also regulate normal HSCs, identifying specific, dominantly acting intrinsic factors could help in the development of novel therapeutic approaches. Here we have reviewed such dominantly acting intrinsic factors governing quiescence vis-a-vis activation of the HSCs in the face of external forces acting on them. For brevity, we have restricted our review to the articles dealing with adult HSCs of human and mouse origin that have been published in the last 10 years. Graphical abstract Hematopoietic stem cells (HSCs) are closely associated with various stromal cells in their microenvironment and, thus, constantly receive signaling cues from them. The illustration depicts some dominantly acting intrinsic or cell-autonomous factors operative in the HSCs. These fall into various categories, such as epigenetic regulators, transcription factors, cell cycle regulators, tumor suppressor genes, signaling pathways, and metabolic regulators, which counteract the outcome of extrinsic signaling exerted by the HSC niche.