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

Abstract

Hematopoietic stem cells (HSCs) possess two important properties such as self-renewal and differentiation. These properties of HSCs are maintained through hematopoiesis. This process gives rise to two subpopulations, long-term and short-term HSCs, which have become a popular convention for treating various hematological disorders. The clinical application of HSCs is bone marrow transplant in patients with aplastic anemia, congenital neutropenia, sickle cell anemia, thalassemia, or replacement of damaged bone marrow in case of chemotherapy. The self-renewal attribute of HSCs ensures long-term hematopoiesis post-transplantation. However, HSCs need to be infused in large numbers to reach their target site and meet the demands since they lose their self-renewal capacity after a few passages. Therefore, a more in-depth understanding of ex vivo HSCs expansion needs to be developed to delineate ways to enhance the self-renewability of isolated HSCs. The multifaceted self-renewal process is regulated by factors, including transcription factors, miRNAs, and the bone marrow niche. A developed classical hierarchical model that outlines the hematopoiesis in a lineage-specific manner through in vivo fate mapping, barcoding, and determination of self-renewal regulatory factors are still to be explored in more detail. Thus, an in-depth study of the self-renewal property of HSCs is essentially required to be utilized for ex vivo expansion. This review primarily focuses on the Hematopoietic stem cell self-renewal pathway and evaluates the regulatory molecular factors involved in considering a targeted clinical approach in numerous malignancies and outlining gaps in the current knowledge.

Aging drives Tet2 +/− clonal hematopoiesis via IL-1 signaling

“…Importantly, this higher proliferative response in IL-1α-treated Tet2 +/-HSCs could not be clearly attributed to differences in gene expression of IL-1 pathway members (Supplemental Figure 5B). Having observed that Tet2 +/-HSPCs maintain a higher self-renewal and repopulation capacity upon IL-1α treatment compared to WT counterparts (Figure 4E), we focused the analysis on genes implicated in HSC self-renewal [30][31][32][33][34][35][36][37] . While most genes were significantly downregulated in both WT and Tet2 +/-HSCs HSCs upon chronic IL-1α exposure (22 genes.…”

Multimodal Mapping of Human Lymphopoiesis Reveals B and T/NK/ILC Lineages are Subjected to Cell-IntrinsicversusFlt3L-Dependent Regulation

“…Functional analysis and pattern distribution (Fig. 3F) confirmed that HSCs selectively express genes regulating quiescence (P1, P12: SOCS2, TAL1, HOPX) 32,33 or self-renewal (P9-10: HLF, MLLT3, MEIS1) 34 , as well as early regulators of erythro-megakaryocytic differentiation (P11: AMPD3, MYH10).…”

Insulin-Producing Cells in the Treatment of Type 1 Diabetes: A Literature Review

“…The bone marrow contains a heterogeneous population of progenitor cells, among which hematopoietic and mesenchymal stem cells play a leading role [4]. The direct isolation of these cells from the bone marrow is a direct aspiration of the ilium contents followed by passages through needles of decreasing diameter in order to create a suspension of cells and separate two germ fractions according to their ability to quickly adhere acquiring a fibroblast-like structure corresponding to mesenchymal stem cells.…”