Revisiting hematopoiesis: applications of the bulk and single-cell transcriptomics dissecting transcriptional heterogeneity in hematopoietic stem cells.

Hematopoietic system (HS) is one of the most unique, adaptive and comprehensive developmental systems on which various other body systems relies on. It consists of a central pool of multipotent hematopoietic stem cells (HSCs) differentiating into lymphoid and myeloid lineage by series of gradual loss of stemness potential. Thus, this highly coordinated phenomenon of blood cell renewal ensures robust immunity and limits autoimmunity. Any disease, chronic infection or stress interrupts HS homeostasis and breaks HSCs' dormancy, thereby activating HSCs to meet the peripheral demand for different immune cells via their expansion and differentiation into more lineage-restricted progenitors, primarily within the bone marrow (BM) in adult life. Therefore, a greater understanding of the overall regulatory landscape of HSC homeostasis and their perturbations is critical for dissecting protective immunity versus autoimmunity. Recent advancements in next-generation sequencing (NGS) viz genomic, transcriptomic, epigenomic and proteogenomic methods at bulk as well as single-cell levels have increased our apprehension for HSC working model. In this review, we discussed the recent findings and computational methods used to unravel the new HSC model revised over the classical model.