Polarized expression of bone morphogenetic protein-4 in the human aorta-gonad-mesonephros region

Polarized expression of bone morphogenetic protein-4 in the human aorta-gonad-mesonephros region
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DOI:
10.1182/blood.v96.4.1591.h8001591_1591_1593
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发表时间:
2000-08-15
期刊:
影响因子:
20.3
通讯作者:
Thrasher, AJ
Thrasher, AJ
中科院分区:
医学1区
文献类型:
--
作者:
Marshall, CJ;Kinnon, C;Thrasher, AJ

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在哺乳动物中,永久性造血干细胞(HSC)首先来源于胚胎主动脉旁内脏胸膜区域内的中胚层细胞,该区域称为腹主动脉-性腺-中肾(AGM)。在该区域内,HSC被认为来自位于背主动脉的腹侧壁中的成血管细胞前体。然而,调控HSC体内发育的因子在很大程度上仍是未知的,骨形态发生蛋白(BMP)-4,生长因子的转化生长因子β(TGF-β)超家族的成员,是一种有效的腹侧化因子,并且已经在许多系统中涉及胚胎中胚层细胞向造血命运的定型。在人AGM中,我们发现BMP-4在主动脉内造血簇下的密集细胞区域中以高水平表达,并且具有显著的极性。相反,TGF-β 1主要由簇内的造血细胞表达。这些发现暗示BMP-4和TGF-β 1都参与了人AGM造血的启动和调节。此外,BMP-4表达的分布高度暗示了在体内来自胚胎中胚层的人造血细胞的特化中的直接作用。(血。2000;96:1591-1593)(C)2000由美国血液学学会。
In the mammal, definitive hematopoietic stem cells (HSCs) are first derived from mesodermal cells within a region of the embryonic para-aortic splanchnopleura known as the aorta-gonad-mesonephros (AGM), Within this region, HSCs are thought to arise from hemangioblast precursors located in the ventral wall of the dorsal aorta. However, the factors that regulate HSC development in vivo are still largely unknown, Bone morphogenetic protein (BMP)-4, a member of the transforming growth factor beta (TGF-beta) superfamily of growth factors, is a potent ventralizing factor and has been implicated in the commitment of embryonic mesodermal cells to a hematopoietic fate in a number of systems. In the human AGM, we find that BMP-4 is expressed at high levels, and with striking polarity, in a region of densely packed cells underlying intra-aortic hematopoietic clusters. In contrast, TGF-beta 1 is expressed predominantly by hematopoietic cells within the clusters. These findings implicate both BMP-4 and TGF-beta 1 in the initiation and regulation of hematopoiesis in the human AGM, Furthermore, the distribution of BMP-4 expression is highly suggestive of a direct role in the specification of human hematopoietic cells from embryonic mesoderm in vivo.(Blood. 2000;96:1591-1593) (C) 2000 by The American Society of Hematology.