Sonic Hedgehog Regulates Early Human Thymocyte Differentiation by Counteracting the IL-7-Induced Development of CD34+ Precursor Cells1
Sonic Hedgehog Regulates Early Human Thymocyte Differentiation by Counteracting the IL-7-Induced Development of CD34+ Precursor Cells1
复制标题
Sonic Hedgehog 通过抵消 IL-7 诱导的 CD34 前体细胞发育来调节早期人类胸腺细胞分化1
作者：
Cruz Gutiérrez;R. Sacedón;Carmen Hernández;Teresa Cejalvo;T. Crompton;A. Zapata;A. Varas;Á. Vicente
Hedgehog（Hh）信号分子家族通常通过调节细胞分化和增殖在许多组织的发育中起作用。最近的研究结果表明，Hh信号通路的不同组分在人胸腺中表达。在这项研究中，我们调查的潜在作用的Sonic刺猬（Shh）在人胸腺内T细胞成熟。结果显示，Hh受体的两种组分（Patched和Smoothened）的表达主要限于定向为T细胞谱系的CD 34+前体细胞。Shh显著增加调节bcl-2和bax蛋白表达的CD 34 + T细胞前体的存活率，并且也抑制它们的增殖。用Shh处理嵌合的人-小鼠胎儿胸腺器官培养物导致胸腺细胞分化停滞和CD 34+祖细胞的积累。这种作用主要归因于Shh对抗IL-7诱导的CD 34+细胞增殖和分化的能力。Shh下调前体细胞群中IL-7 R以及基质衍生因子-1趋化因子受体CXCR 4的表达，并抑制IL-7依赖性STAT 5磷酸化。因此，Shh可能作为胸腺内CD 34+前体细胞的维持因子。
The Hedgehog (Hh) family of signaling molecules normally functions in the development of numerous tissues by regulating cellular differentiation and proliferation. Recent results have demonstrated that the different components of the Hh signaling pathway are expressed in the human thymus. In this study, we investigate the potential role of Sonic hedgehog (Shh) in human intrathymic T cell maturation. Results show that the expression of the two components of the Hh receptor, Patched and Smoothened, is mostly restricted to CD34+ precursor cells that are committing to the T cell lineage. Shh significantly increased the viability of CD34+ T cell precursors modulating bcl-2 and bax protein expression, and also inhibited their proliferation. The treatment of chimeric human-mouse fetal thymus organ cultures with Shh resulted in an arrested thymocyte differentiation and an accumulation of CD34+ progenitor cells. This effect was mainly attributed to the ability of Shh to counteract the IL-7-induced proliferation and differentiation of CD34+ cells. Shh down-regulated in the precursor cell population the expression of IL-7R as well as stromal-derived factor-1 chemokine receptor, CXCR4, and inhibited IL-7-dependent STAT5 phosphorylation. Therefore, Shh may function as a maintenance factor for intrathymic CD34+ precursor cells.
DOI：
10.1242/dev.127.22.4905
发表时间：
2000
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hebrok,M;Kim,SK;StJacques,B;McMahon,AP;Melton,DA
通讯作者：
Melton,DA
Gli 蛋白编码上下文相关的积极和消极功能：对发育和疾病的影响。
DOI：
10.1242/dev.126.14.3205
发表时间：
1999
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
RuiziAltaba,A
通讯作者：
RuiziAltaba,A