Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling
Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling
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DOI：
10.1006/bcmd.2000.0318
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发表时间：
2000-08-01
影响因子：
2.3
通讯作者：
Dannawi, H
中科院分区：
文献类型：
--
作者：
Detmer, K;Walker, AN;Dannawi, H
成体造血分化是一个发育过程，采用许多与胚胎发生相同的分子机制。为了探讨hedgehog信号传导参与造血分化控制的可能性，我们筛选了一组人类白血病细胞系，以检测其表达情况，即hedgehog配体的受体和辅助受体Smoothened，在多个细胞系中均发现表达，并且在正常骨髓中检测到Patched1表达，细胞系中骨髓分化的诱导下调了这两个基因的表达。当正常骨髓单核细胞在存在10μM环杷明的半固体培养基中生长时，粒细胞/单核细胞谱系的集落的发育在数量和形态上均不受影响。然而，红细胞集落的数量显着减少（P < 0.01）。此外，在那些确实形成的红细胞集落中，血红蛋白化相对于对照显着延迟。造血祖细胞与 Shh-N 和 GM-CSF 一起孵育导致粒细胞/单核细胞集落增加 (P < 0.01)；该增加被环杷明阻断。造血祖细胞与Shh-N和干细胞因子一起孵育会产生更大的红系集落。这些结果表明刺猬信号通路的元件参与造血分化的控制。 (C) 2000 年学术出版社。
Adult hematopoietic differentiation is a developmental process that employs many of the same molecular mechanisms as embryogenesis. To explore the possibility that hedgehog signaling is involved in the control of hematopoietic differentiation, we screened a panel of human leukemia cell lines for the expression of Patched1 and Smoothened, the receptor and coreceptor for hedgehog ligands, Expression was found in multiple cell lines, and Patched1 expression was detected in normal marrow, Induction of myeloid differentiation in cell lines downregulated expression of both genes. When normal marrow mononuclear cells were grown in semisolid medium in the presence of 10 muM cyclopamine, development of colonies of,granulocytic/monocytic lineage was unaffected in terms of both number and morphology. The number of erythroid colonies, however, was significantly reduced (P < 0.01). Furthermore, hemoglobinization was substantially delayed relative to controls in those erythroid colonies that did form. Incubation of hematopoietic progenitors with Shh-N and GM-CSF resulted in increased granulocyte/monocyte colonies (P < 0.01); the increase was blocked by cyclopamine. Incubation of hematopoietic progenitors with Shh-N and stem cell factor resulted in larger erythroid colonies. These results suggest that elements of the hedgehog signaling pathway are involved in the control of hematopoietic differentiation. (C) 2000 Academic Press.