Mann Zoya, Sengar Manisha, Verma Yogesh Kumar, Rajalingam Raja, Raghav Pawan Kumar
Independent Researcher, New Delhi, India.
Department of Zoology, Deshbandhu College, University of Delhi, Delhi, India.
Front Cell Dev Biol. 2022 Mar 24;10:664261. doi: 10.3389/fcell.2022.664261. eCollection 2022.
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 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 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 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.
造血干细胞(HSCs)具有自我更新和分化这两个重要特性。造血干细胞的这些特性通过造血作用得以维持。这个过程产生了两个亚群,即长期和短期造血干细胞,它们已成为治疗各种血液系统疾病的常用方法。造血干细胞的临床应用是对再生障碍性贫血、先天性中性粒细胞减少症、镰状细胞贫血、地中海贫血患者进行骨髓移植,或在化疗情况下替代受损的骨髓。造血干细胞的自我更新特性确保了移植后的长期造血。然而,由于造血干细胞在传代几次后会丧失自我更新能力,因此需要大量注入才能到达靶位点并满足需求。因此,需要更深入地了解造血干细胞的扩增,以探寻增强分离出的造血干细胞自我更新能力的方法。多方面的自我更新过程受多种因素调控,包括转录因子、微小RNA和骨髓微环境。一个已建立的经典层级模型通过命运图谱、条形码技术以及自我更新调节因子的确定,以谱系特异性方式勾勒了造血过程,但仍有待更详细地探索。因此,深入研究造血干细胞的自我更新特性对于其扩增的应用至关重要。本综述主要聚焦于造血干细胞自我更新途径,并评估在众多恶性肿瘤中考虑靶向临床方法时涉及的调控分子因素,同时概述当前知识中的空白。