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Shh 信号调节肾上腺皮质的发育,并鉴定类固醇生成谱系的祖细胞。

Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages.

机构信息

William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom.

出版信息

Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21185-90. doi: 10.1073/pnas.0909471106. Epub 2009 Dec 1.

DOI:10.1073/pnas.0909471106
PMID:19955443
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2786892/
Abstract

The adrenal cortex is a critical steroidogenic endocrine tissue, generated at least in part from the coelomic epithelium of the urogenital ridge. Neither the intercellular signals that regulate cortical development and maintenance nor the lineage relationships within the adrenal are well defined. We have explored adrenal Shh activity and found that Shh is expressed in relatively undifferentiated steroidogenic cells, which signal to the overlying capsule and subjacent nonsteroidogenic mesenchyme cells that we also find are progenitors of steroidogenic lineages. Shh-expressing cells also generate all steroidogenic cell types, but not nonsteroidogenic ones. Shh mutant adrenals have a thin capsule and small cortex. Our findings both support a novel dual lineage, Shh-independent and Shh-dependent, model of adrenocortical development, and identify distinct populations of adrenocortical progenitor and candidate stem cells.

摘要

肾上腺皮质是一种重要的甾体生成内分泌组织,至少部分来源于尿生殖嵴的体腔上皮。调节皮质发育和维持的细胞间信号以及肾上腺内的谱系关系都尚未明确。我们已经研究了肾上腺 Shh 活性,发现 Shh 在相对未分化的甾体生成细胞中表达,这些细胞向覆盖的包膜和下方的非甾体生成间充质细胞发出信号,我们还发现这些细胞也是甾体生成谱系的祖细胞。Shh 表达细胞也产生所有甾体生成细胞类型,但不产生非甾体生成细胞类型。Shh 突变的肾上腺有一个薄的包膜和小的皮质。我们的研究结果既支持了一个新的双重谱系(Shh 非依赖性和 Shh 依赖性)的肾上腺皮质发育模型,又确定了肾上腺皮质祖细胞和候选干细胞的不同群体。

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Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21185-90. doi: 10.1073/pnas.0909471106. Epub 2009 Dec 1.
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本文引用的文献

1
Targeted disruption of Sonic Hedgehog in the mouse adrenal leads to adrenocortical hypoplasia.对小鼠肾上腺中 Sonic Hedgehog 进行靶向破坏会导致肾上腺皮质发育不全。
Genesis. 2009 Sep;47(9):628-37. doi: 10.1002/dvg.20532.
2
Developmental links between the fetal and adult zones of the adrenal cortex revealed by lineage tracing.通过谱系追踪揭示肾上腺皮质胎儿区与成人区之间的发育联系。
Mol Cell Biol. 2008 Dec;28(23):7030-40. doi: 10.1128/MCB.00900-08. Epub 2008 Sep 22.
3
Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex.在表达Sf1的细胞中对β-连环蛋白进行靶向破坏会损害肾上腺皮质的发育和维持。
Development. 2008 Aug;135(15):2593-602. doi: 10.1242/dev.021493. Epub 2008 Jul 3.
4
Hedgehog signalling in endocrine development and disease.刺猬信号通路在内分泌发育与疾病中的作用
J Endocrinol. 2008 Sep;198(3):439-50. doi: 10.1677/JOE-08-0161. Epub 2008 Jun 4.
5
Melanocortin 2 receptor is required for adrenal gland development, steroidogenesis, and neonatal gluconeogenesis.促黑素细胞激素2受体是肾上腺发育、类固醇生成和新生儿糖异生所必需的。
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18205-10. doi: 10.1073/pnas.0706953104. Epub 2007 Nov 7.
6
A global double-fluorescent Cre reporter mouse.一种全球双荧光Cre报告基因小鼠。
Genesis. 2007 Sep;45(9):593-605. doi: 10.1002/dvg.20335.
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Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons.脑室下区的刺猬信号通路对于干细胞的维持和新生神经元的迁移都是必需的。
J Neurosci. 2007 May 30;27(22):5936-47. doi: 10.1523/JNEUROSCI.1040-07.2007.
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Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage.肾上腺发育由Cited2和Wt1通过调节Sf-1剂量启动。
Development. 2007 Jun;134(12):2349-58. doi: 10.1242/dev.004390.
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Adrenocortical cells with stem/progenitor cell properties: recent advances.具有干细胞/祖细胞特性的肾上腺皮质细胞:最新进展
Mol Cell Endocrinol. 2007 Feb;265-266:10-6. doi: 10.1016/j.mce.2006.12.028. Epub 2007 Jan 19.
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Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone.小鼠体内的肾上腺20α-羟基类固醇脱氢酶可分解孕酮和11-脱氧皮质酮,且仅存在于X区。
Endocrinology. 2007 Mar;148(3):976-88. doi: 10.1210/en.2006-1100. Epub 2006 Nov 22.