About this Research Topic
The hematopoietic system consists of several different cell types broadly classified into red blood cells (erythrocytes) and white blood cells (lymphocytes, monocytes, neutrophils, megakaryocytes, etc.). These blood cells, largely responsible for oxygen circulation, immune protection, and wound healing, have one of the highest turnover rates in the human body. Hence, studies on hematopoietic stem cells (HSCs) – self-renewing, multipotent stem cells capable of generating and, thus, replenishing all myeloid and lymphoid lineages – are of utmost importance. HSCs are classified into long-term HSCs (LT-HSC) and short-term HSCs (ST-HSC). The former class of HSCs are true stem cells capable of complete self-renewal and regeneration of all blood sub-types, while the latter kind, although capable of proliferation, seem to be more lineage-restricted.
Extensive research over the past few decades has led the hematopoietic stem cell transplantation as an actively used procedure for the treatment of various hematologic disorders. However, the complex mechanisms that govern the development and maintenance of such stem cells in the human body continue to be uncovered. The roles of transcription factors, their associated chromatin regulators, and intracellular/extracellular signaling pathways are key in this regard and constitute active areas of research. Several transcription factors (e.g., GATA2, FLI1, PU.1, RUNX1, LMO2, TAL1, ERG, Gfi1, Bmi1, and others) essential for HSC development and/or maintenance have been identified. These transcription factors communicate with the extracellular environment through signaling pathways. Notch-GLI, BMP-SMAD, WNT-TCF/LEF, PGE2-CREB, and Hedgehog-HES-mediated signaling pathways have been shown to be active in maintaining HSCs under normal and stress-hematopoiesis.
Despite the recent and rapid advances in elucidating the role of various transcription factors in HSC specification, maintenance, transitions, and function, much remains to be learned. One important aspect regarding the complex regulatory networks of transcription factors is the integration of intracellular and extracellular cues to produce, maintain, and fine-tune HSC functions at different stages and contexts. Active research, spearheaded by current technological advancements and newer scientific approaches, is required to significantly contribute to our understanding of the role of transcription factors in HSC formation, renewal, and maintenance.
This Research Topic will include scientific materials on hematopoietic transcription factors, related chromatin regulators, and their networks in generating and maintaining HSCs at multiple stages and anatomical locations. It will focus on showcasing both new transcription factors and their ancillary factors as well as emerging molecular interactions between known and novel factors and the integration of transcriptional processes and chromatin changes with relevant signaling pathways. The goal of this Research Topic is to highlight new and significant insights into HSC biology as well as refine and/or redefine existing concepts regarding this critical and still somewhat enigmatic cell type. How these mechanisms could be perturbed in various hematologic diseases will also be discussed under this Topic.
Keywords: hematopoietic stem cell, transcription, gene regulation, hematologic disease, signaling
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