First blood: the endothelial origins of hematopoietic progenitors.

First blood: the endothelial origins of hematopoietic progenitors.
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DOI:
10.1007/s10456-021-09783-9
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发表时间:
2021-05
期刊:
影响因子:
9.8
通讯作者:
Ruhrberg C
Ruhrberg C
中科院分区:
医学1区
文献类型:
--
作者:
Canu G;Ruhrberg C

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脊椎动物胚胎中的造血发生在时间和空间重叠波中,靠近血管内皮细胞。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,通过内皮细胞向造血细胞的转变(EHT),卵黄囊和胚胎内造血内皮细胞产生连续的造血波。在EHT期间,内皮和造血转录程序被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,其在迁移到肝脏时分化成胎儿血细胞,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,这些造血干细胞植入胎儿肝脏,然后植入骨髓以维持成人造血。最近的研究已经在动物模型中确定了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,人多能干细胞已经能够模拟胎儿人造血,并已开始产生再生医学临床感兴趣的细胞类型。
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.
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