哺乳动物造血干细胞（HSC）从主要胚胎动脉的造血内皮中产生。 HSC 经历了一个复杂的旅程，首先迁移到胎儿肝脏 (FL)，然后从那里迁移到胎儿骨髓 (FBM)，它们在成年后大部分停留在骨髓中。在此过程中，产生了一批成体造血干细胞，维持终生造血功能。多种细胞成分支持 HSC 成熟和扩增，并调节其对环境和发育线索的反应。虽然成人 HSC 生态位在过去二十年中得到了广泛的研究，但对主要胚胎动脉、FL、FBM 和围产期骨髓 (BM) 中存在的生态位的描述却很少。最近的研究强调了 FL、FBM 和成人 BM 生态位之间的重要差异，并强调炎症、微生物群和激素因素在调节 HSC 及其生态位中发挥的重要作用。我们对目前对个体发育过程中这些重要细胞微环境的理解进行了回顾。我们主要关注小鼠，作为最广泛使用的研究模型，并在可能的情况下纳入其他脊椎动物（包括鸟类、斑马鱼和人类）的相关见解。全面了解这些过程对于了解儿童白血病的最早起源和实现再生医学的多个目标至关重要，例如在体外模拟造血干细胞的发育，以产生造血干细胞，用于白血病、化疗、骨髓衰竭后的广泛移植目的。以及基于 HSC 的基因治疗。版权所有 © 2024 Sánchez-Lanzas、Jiménez-Pompa 和 Ganuza。

Mammalian hematopoietic stem cells (HSCs) emerge from the hemogenic endothelium in the major embryonic arteries. HSCs undergo a complex journey first migrating to the fetal liver (FL) and from there to the fetal bone marrow (FBM), where they mostly remain during adult life. In this process, a pool of adult HSCs is produced, which sustains lifelong hematopoiesis. Multiple cellular components support HSC maturation and expansion and modulate their response to environmental and developmental cues. While the adult HSC niche has been extensively studied over the last two decades, the niches present in the major embryonic arteries, FL, FBM and perinatal bone marrow (BM) are poorly described. Recent investigations highlight important differences among FL, FBM and adult BM niches and emphasize the important role that inflammation, microbiota and hormonal factors play regulating HSCs and their niches. We provide a review on our current understanding of these important cellular microenvironments across ontogeny. We mainly focused on mice, as the most widely used research model, and, when possible, include relevant insights from other vertebrates including birds, zebrafish, and human. Developing a comprehensive picture on these processes is critical to understand the earliest origins of childhood leukemia and to achieve multiple goals in regenerative medicine, such as mimicking HSC development in vitro to produce HSCs for broad transplantation purposes in leukemia, following chemotherapy, bone marrow failure, and in HSC-based gene therapy.Copyright © 2024 Sánchez-Lanzas, Jiménez-Pompa and Ganuza.