Hematopoietic Stem Cell Molecular Targets and Factors Essential for Hematopoiesis

Abstract

Hematopoietic Stem Cells (HSCs) gained popularity in the area of medicine because of its remarkable potential to cure an enormous range of human diseases. These stem cells are used for therapeutic purposes for its regenerative capacity and possessed hematopoiesis. This process reflects characteristic properties, proliferation, and differentiation. These behaviors are a result of protein-mediated molecular interactions. However, these molecular interactions underlying are yet to be explored. Thus, the present review focuses on the molecular basis of hematopoiesis wherein, significant molecular interactions which regulate differentiation and proliferation has been discussed. Primarily, we have addressed the role of cytokines, transcription factors, proliferation, and pathways involved in hematopoiesis. Also, relationship with multiple cytokines, small molecules, nutrients, cell-cell contacts and the extracellular matrix which impel a cascade of signals that controls stem cell behavior and fate has been summarized in this review. A large number of datasets of hematopoiesis is publicly available to researchers around the world. This review also provides databases on hematopoiesis which will be very beneficial in facilitating common analysis, basic research and clinical diagnosis for the treatment of blood-related disorders.

Hematopoietic Stem Cell Factors: Their Functional Role in Self-Renewal and Clinical Aspects

“…Similarly, c-Myb is a key self-renewal regulator in the early stages of HSCs development which acts in conjunction with PU.1 to enhance proliferation in the earlier set of HSCs, as reported in mice and human studies. The decrease in c-Myb expression leads to HSCs lineage commitment towards erythroid cells ( Soza-Ried et al, 2010 ; Raghav and Gangenahalli, 2018 ). Therefore, it indicates that both these isoforms regulate cell fate in the early stages of the cell cycle.…”

“…However, further quantification revealed that these progenitors possess self-renewal potential lesser than that of LT-HSCs, in addition to their transiting nature ( Höfer and Rodewald, 2018 ; Busch et al, 2015 ). However, myeloid progenitor cells lack self-renewal since it is tightly regulated by various endogenous molecules, including transcription factors (TFs), cytokines, niche conditions, and epigenetic modifiers ( Table 1 ) ( Sun et al, 2014 ; Busch et al, 2015 ; Höfer et al, 2016 ; Raghav and Gangenahalli, 2018 ). Mx1-Cre is another inducible tool in which Cre recombinase is activated under the Mx1 promoter by either synthetically designed dsRNA that induces production of interferons IFN-α and IFN-β, or other immunostimulants like polyinosinic: polycytidylic acid (pIpC) ( Joseph et al, 2013 ).…”

PU.1 Mimic Synthetic Peptides Selectively Bind with GATA-1 and Allow c-Jun PU.1 Binding to Enhance Myelopoiesis

“… 1 Thus, a strengthened immune system enriched with myeloid cells is needed, which can be accomplished by precise regulation of transcription factor (TF) such as Purine rich box 1 (PU.1) (31kDa), GATA-1 (42.7 kDa) and c-Jun (41.9 kDa). 2 …”

“… 3 PU.1 protein levels within the hematopoietic stem cells (HSCs) are regulated by NF-κB signaling, activated by Tumor Necrosis Factor (TNF). 4 Although, GATA-1 plays a major role in the later stages of erythropoiesis, 2 more so in the development of hematopoietic precursor cells (HPCs) committed to the erythroid lineage, primarily through Scl–Gata2–Fli1 triad. 5 Other coactivators that facilitate HPC development include Scl/TAL1, LDB1, and LMO2.…”

“…1 Thus, a strengthened immune system enriched with myeloid cells is needed, which can be accomplished by precise regulation of transcription factor (TF) such as Purine rich box 1 (PU.1) (31kDa), GATA-1 (42.7 kDa) and c-Jun (41.9 kDa). 2 PU.1 is an ETS family TF, encoded by Spi-1 gene, that by binding to PU-box acts as a transcriptional activator involved in differentiation and activation of macrophages, dendritic cells and B-cells. It plays a significant role in early stages of precursor T-cell development and is an established antagonist of erythropoiesis.…”