Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation
Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation
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DOI：
10.1038/84282
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发表时间：
2001-02-01
影响因子：
30.5
通讯作者：
Bhatia, M
中科院分区：
文献类型：
--
作者：
Bhardwaj, G;Murdoch, B;Bhatia, M
胚胎发生时，中胚层产生的干细胞池开始造血。然而，调节造血干细胞扩张的因素却知之甚少。我们在这里表明，细胞因子诱导的原始人类造血细胞增殖可以被hedgehog （Hh）抗体抑制。相反，在免疫缺陷小鼠中检测到，Sonic hedgehog （Shh）处理诱导了多能人造血再填充细胞的扩增。Noggin是骨形态发生蛋白4 （BMP-4）的特异性抑制剂，能够以与抗hh相似的方式抑制sh诱导的增殖；然而，抗hh对bmp -4诱导的增殖没有影响。我们的研究表明Shh通过依赖于下游BMP信号的机制调节原始造血细胞。
A pool of stem cells that arise from the mesoderm during embryogenesis initiates hematopoiesis. However, factors that regulate the expansion of blood stem cells are poorly understood. We show here that cytokine-induced proliferation of primitive human hematopoietic cells could be inhibited with antibodies to hedgehog (Hh). Conversely, Sonic hedgehog (Shh) treatment induced the expansion of pluripotent human hematopoietic repopulating cells detected in immunodeficient mice. Noggin, a specific inhibitor of bone morphogenetic protein 4 (BMP-4), was capable of inhibiting Shh-induced proliferation in a similar manner to anti-Hh; however, anti-Hh had no effect on BMP-4-induced proliferation. Our study shows that Shh functions as a regulator of primitive hematopoietic cells via mechanisms that are dependent on downstream BMP signals.