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First blood: the endothelial origins of hematopoietic progenitors
Angiogenesis ( IF 9.8 ) Pub Date : 2021-03-30 , DOI: 10.1007/s10456-021-09783-9
Giovanni Canu 1 , Christiana Ruhrberg 1
Affiliation  

Hematopoiesis in vertebrate embryos occurs in temporally and spatially overlapping waves in close proximity to blood vascular endothelial cells. Initially, yolk sac hematopoiesis produces primitive erythrocytes, megakaryocytes, and macrophages. Thereafter, sequential waves of definitive hematopoiesis arise from yolk sac and intraembryonic hemogenic endothelia through an endothelial-to-hematopoietic transition (EHT). During EHT, the endothelial and hematopoietic transcriptional programs are tightly co-regulated to orchestrate a shift in cell identity. In the yolk sac, EHT generates erythro-myeloid progenitors, which upon migration to the liver differentiate into fetal blood cells, including erythrocytes and tissue-resident macrophages. In the dorsal aorta, EHT produces hematopoietic stem cells, which engraft the fetal liver and then the bone marrow to sustain adult hematopoiesis. Recent studies have defined the relationship between the developing vascular and hematopoietic systems in animal models, including molecular mechanisms that drive the hemato-endothelial transcription program for EHT. Moreover, human pluripotent stem cells have enabled modeling of fetal human hematopoiesis and have begun to generate cell types of clinical interest for regenerative medicine.



中文翻译:

第一滴血:造血祖细胞的内皮起源

脊椎动物胚胎中的造血作用发生在靠近血管内皮细胞的时间和空间上重叠的波中。最初,卵黄囊造血产生原始红细胞、巨核细胞和巨噬细胞。此后,卵黄囊和胚胎内造血内皮通过内皮向造血转变(EHT)产生连续波的确定造血作用。在 EHT 过程中,内皮和造血转录程序紧密地共同调节,以协调细胞身份的转变。在卵黄囊中,EHT 产生红骨髓祖细胞,这些祖细胞在迁移到肝脏后分化成胎儿血细胞,包括红细胞和组织驻留巨噬细胞。在背主动脉中,EHT 产生造血干细胞,这些细胞植入胎儿肝脏,然后植入骨髓以维持成人造血功能。最近的研究已经确定了动物模型中发育中的血管和造血系统之间的关系,包括驱动 EHT 的血液内皮转录程序的分子机制。此外,人类多能干细胞已经能够对人类胎儿造血进行建模,并开始产生再生医学临床感兴趣的细胞类型。

更新日期:2021-03-30
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