Narayan Anand Badhri, Hariom Senthil Kumar, Mukherjee Ayan Prasad, Das Deotima, Nair Aadhira, Nelson Everette Jacob Remington
Department of Integrative Biology, Gene Therapy Laboratory, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, TN, 632 014, India.
Stem Cell Rev Rep. 2025 Apr;21(3):605-628. doi: 10.1007/s12015-025-10843-6. Epub 2025 Jan 9.
Hematopoietic stem cells are a unique population of tissue-resident multipotent cells with an extensive ability to self-renew and regenerate the entire lineage of differentiated blood cells. Stem cells reside in a highly specialized microenvironment with surrounding supporting cells, forming a complex and dynamic network to preserve and maintain their function. The survival, activation, and quiescence of stem cells are largely influenced by niche-derived signals, with aging niche contributing to a decline in stem cell function. Although the role of niche in regulating hematopoiesis has long been established by transplantation studies, limited methods in observing the process in vivo have eluded a detailed understanding of the various niche components. Danio rerio (zebrafish) has emerged as a solution in the past few decades, enabling discovery of cellular interactions, in addition to chemical and genetic factors regulating HSCs. This review reiterates zebrafish as a suitable model for studies on vertebrate embryonic and adult hematopoiesis, delving into this temporally and spatially dissected multi-step process. The critical role played by epigenetic regulators are discussed, along with contributions of the various physiological processes in sustaining the stem cell population. Stem cell niche transcends mere knowledge acquisition, assuring scope in cell therapy, organoid cultures, aging research, and clinical applications including bone marrow transplantation and cancer. A better understanding of the various niche components could also leverage therapeutic efforts to drive differentiation of HSCs from pluripotent progenitors, sustain stemness in laboratory cultures, and improve stem cell transplantation outcomes.
造血干细胞是一群独特的组织驻留多能细胞,具有广泛的自我更新和再生整个分化血细胞谱系的能力。干细胞存在于一个高度特化的微环境中,周围有支持细胞,形成一个复杂而动态的网络来维持和保持它们的功能。干细胞的存活、激活和静止在很大程度上受微环境衍生信号的影响,老化的微环境会导致干细胞功能下降。尽管通过移植研究早已确立了微环境在调节造血中的作用,但体内观察这一过程的方法有限,阻碍了对各种微环境成分的详细了解。在过去几十年中,斑马鱼已成为一种解决方案,除了调节造血干细胞的化学和遗传因素外,还能发现细胞间相互作用。这篇综述重申斑马鱼是研究脊椎动物胚胎和成人造血的合适模型,深入探讨这个在时间和空间上被剖析的多步骤过程。讨论了表观遗传调节因子所起的关键作用,以及各种生理过程对维持干细胞群体的贡献。干细胞微环境不仅仅是知识获取,还确保了细胞治疗、类器官培养、衰老研究以及包括骨髓移植和癌症在内的临床应用的范围。更好地理解各种微环境成分也可以利用治疗手段来驱动多能祖细胞分化为造血干细胞,在实验室培养中维持干性,并改善干细胞移植结果。