T細(xì)胞是在胸腺中產(chǎn)生的一類非常重要的細(xì)胞,，能夠協(xié)調(diào)機(jī)體對癌癥或感染產(chǎn)生的免疫反應(yīng),。在一項(xiàng)最新研究中，來自美國貝勒醫(yī)學(xué)院的研究人員領(lǐng)導(dǎo)的一個(gè)研究小組發(fā)現(xiàn)轉(zhuǎn)錄因子Lyl-1是產(chǎn)生能夠變成T細(xì)胞的最早的細(xì)胞所必需的,。相關(guān)研究結(jié)果于2012年7月8日在線發(fā)表在Nature Immunology期刊上,。
論文通訊作者、貝勒醫(yī)學(xué)院干細(xì)胞與再生醫(yī)學(xué)中心主任Margaret Goodell說,，這些最早的祖細(xì)胞(也被稱作早期T細(xì)胞系祖細(xì)胞)是被鑒定為最終變成T細(xì)胞的最為原始的細(xì)胞,。如果沒有Lyl-1，這些早期T細(xì)胞系祖細(xì)胞(early T lineage progenitor cell)中只有少量得以產(chǎn)生,。
Goodell實(shí)驗(yàn)室博士后學(xué)生Fabian Zohren博士發(fā)現(xiàn)缺乏表達(dá)這種轉(zhuǎn)錄因子的基因的小鼠患上T細(xì)胞缺乏癥,，尤其是這些早期祖細(xì)胞數(shù)量特別少。
Goodell說,，“這表明這些早期T細(xì)胞系祖細(xì)胞的產(chǎn)生確實(shí)依賴Lyl-1,。我們認(rèn)為Lyl-1控制著一種允許這些至為重要的祖細(xì)胞存活和增殖的程序。”
這一發(fā)現(xiàn)可能也有助于人們理解一種類型的白血病,，即急性T淋巴細(xì)胞白血病(T-cell acute lymphoblastic leukemia),。研究人員發(fā)現(xiàn)，就這種類型的疾病而言,，癌細(xì)胞類似于這些早期T細(xì)胞系祖細(xì)胞的白血病預(yù)后最差,。此外，這些癌細(xì)胞也有高水平的Lyl-1,。
一種可能的解釋就是患有這種類型的T淋巴細(xì)胞白血病的病人體內(nèi)的T細(xì)胞系祖細(xì)胞繼續(xù)表達(dá)Lyl-1,，因而繼續(xù)增殖。在早期T細(xì)胞系祖細(xì)胞中過量的Lyl-1能夠阻止早期T細(xì)胞系祖細(xì)胞分化為有活性的T細(xì)胞,。Goodell說,，在未來，他想測試這種假設(shè),。(生物谷：Bioon.com)
本文編譯自Transcription factor Lyl-1 critical in producing early T-cell progenitors
doi: 10.1038/ni.2365
PMC:
PMID:
The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors
Fabian Zohren, George P Souroullas, Min Luo, Ulrike Gerdemann, Maria R Imperato, Nicola K Wilson, Berthold Göttgens, Georgi L Lukov & Margaret A Goodell
Thymopoiesis depends on the recruitment and expansion of bone marrow–derived progenitor populations; tight regulation of these processes is required for maintenance of the homeostasis of the T lineage. Lyl-1, a transcription factor that regulates hematopoietic progenitors, is expressed in thymocyte progenitors until T cell commitment. Here we demonstrate a requirement for Lyl-1 in lymphoid specification and the maintenance of early T lineage progenitors (ETPs). Lyl-1 deficiency resulted in profound defects in the generation of lymphoid-primed multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs) and ETPs. Lyl-1-deficient ETPs and thymocyte progenitors at the CD4−CD8− double-negative 2 (DN2) stage showed more apoptosis, blocked differentiation and impaired population expansion. We identified Gfi1 as a critical transcriptional target of Lyl-1-mediated lymphopoiesis of T cells. Thus, Lyl-1 is a pivotal component of a transcriptional program that controls the lymphoid specification and maintenance of ETPs.
