Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Cell Rep. 2023 Mar 28;42(3):112239. doi: 10.1016/j.celrep.2023.112239. Epub 2023 Mar 11.
It is widely believed that hematopoiesis after birth is established by hematopoietic stem cells (HSCs) in the bone marrow and that HSC-independent hematopoiesis is limited only to primitive erythro-myeloid cells and tissue-resident innate immune cells arising in the embryo. Here, surprisingly, we find that significant percentages of lymphocytes are not derived from HSCs, even in 1-year-old mice. Instead, multiple waves of hematopoiesis occur from embryonic day 7.5 (E7.5) to E11.5 endothelial cells, which simultaneously produce HSCs and lymphoid progenitors that constitute many layers of adaptive T and B lymphocytes in adult mice. Additionally, HSC lineage tracing reveals that the contribution of fetal liver HSCs to peritoneal B-1a cells is minimal and that the majority of B-1a cells are HSC independent. Our discovery of extensive HSC-independent lymphocytes in adult mice attests to the complex blood developmental dynamics spanning the embryo-to-adult transition and challenges the paradigm of HSCs exclusively underpinning the postnatal immune system.
人们普遍认为，出生后的造血是由骨髓中的造血干细胞（HSCs）建立的，而 HSC 非依赖性造血仅限于胚胎中出现的原始红髓细胞和组织驻留固有免疫细胞。在这里，令人惊讶的是，我们发现即使在 1 岁的小鼠中，仍有相当大比例的淋巴细胞不是来自 HSCs。相反，从胚胎第 7.5 天（E7.5）到 E11.5 内皮细胞，会发生多波造血，这些内皮细胞同时产生 HSCs 和淋巴祖细胞，构成成年小鼠中许多层适应性 T 和 B 淋巴细胞。此外，HSC 谱系追踪显示，胎儿肝脏 HSCs 对腹膜 B-1a 细胞的贡献微乎其微，而大多数 B-1a 细胞是 HSC 非依赖性的。我们在成年小鼠中发现广泛存在的 HSC 非依赖性淋巴细胞，证明了胚胎到成年过渡期间复杂的血液发育动态，并挑战了 HSCs 完全支撑后天免疫系统的范式。
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