（封面圖片：胚胎干細(xì)胞以及組織特異性干細(xì)胞的基因模塊圖譜,。圖片提供：David J. Wong以及Howard Y. Chang）
自我更新（self-renewal）是干細(xì)胞和癌細(xì)胞的共同特征,，但是對(duì)于它們是否擁有共同的干性（stemness）程序，科學(xué)界一直存在爭(zhēng)議,。目前的干細(xì)胞模型認(rèn)為,，有少量的祖細(xì)胞維持著自我更新的能力以及組織的結(jié)構(gòu)。胚胎干細(xì)胞（embryonic stem cell,，ESC）和成體干細(xì)胞自我更新以及發(fā)育出多種細(xì)胞的能力構(gòu)成了“干性”的最基本定義,。而大量的證據(jù)表明，腫瘤同樣存在相應(yīng)的腫瘤干細(xì)胞，因此,，發(fā)現(xiàn),、消滅這些細(xì)胞對(duì)于診斷和治療癌癥就很重要。
在2008年4月10日出版的《細(xì)胞—干細(xì)胞》（Cell Stem Cell）上,，來自美國(guó)和以色列的一組科學(xué)家發(fā)表文章稱,，他們成功地建立了一種基因模塊圖譜（gene module map），這種圖譜能將胚胎干細(xì)胞,、成年組織干細(xì)胞,、以及人類癌癥組織的轉(zhuǎn)錄程序系統(tǒng)連接起來。圖譜還揭示了兩種區(qū)分胚胎干細(xì)胞和成年組織干細(xì)胞的主要基因模塊,。類胚胎干細(xì)胞轉(zhuǎn)錄程序在多種人類上皮癌（epithelial cancers）中都得到激活,，并且能預(yù)測(cè)轉(zhuǎn)移和死亡率。腫瘤基因c-Myc能重新激活正常和癌變細(xì)胞中的類胚胎干細(xì)胞程序,。在Ras和IκBα轉(zhuǎn)化而來的人類原代角質(zhì)形成細(xì)胞（primary human keratinocytes）中,，c-Myc會(huì)使得腫瘤起源細(xì)胞（tumor-initiating cell）增加150倍。這種c-Myc增加的腫瘤發(fā)生不受到基因組不穩(wěn)定性（genomic instability）的影響,。因此,，激發(fā)分化成年細(xì)胞中的類胚胎干細(xì)胞轉(zhuǎn)錄程序或許會(huì)誘導(dǎo)癌干細(xì)胞的病態(tài)自我更新發(fā)生。
研究結(jié)果顯示,，類胚胎干細(xì)胞程序不僅僅只是增生信號(hào),。從基因模塊圖譜得到的類胚胎干細(xì)胞程序在各種人類癌癥中得到激發(fā)，并且能預(yù)測(cè)患者死亡率和轉(zhuǎn)移可能,。此外,，科學(xué)家發(fā)現(xiàn)c-Myc除了推動(dòng)細(xì)胞增生外還存在其它作用，但目前研究人員還無法證明類胚胎干細(xì)胞信號(hào)能提供獨(dú)立的診斷價(jià)值,，并且也不清楚類胚胎干細(xì)胞信號(hào)究竟是在少量的腫瘤干細(xì)胞或大量人體癌癥組織中得到表達(dá),。所以作者表示，還需要進(jìn)行進(jìn)一步研究來解決這些問題,。（科學(xué)網(wǎng) 何宏輝/編譯）
生物谷推薦原始出處：
（Cell Stem Cell）,，Vol 2, 333-344, 10 April 2008，David J. Wong, Howard Y. Chang
Module Map of Stem Cell Genes Guides Creation of Epithelial Cancer Stem Cells
David J. Wong,1 Helen Liu,1 Todd W. Ridky,1 David Cassarino,2 Eran Segal,3, and Howard Y. Chang1,
1 Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA
2 Department of Pathology, Stanford University, Stanford, CA 94305, USA
3 Department of Computer Science and Applied Mathematics, Weizmann Institute, Rehovot 76100, Israel
Summary
Self-renewal is a hallmark of stem cells and cancer, but existence of a shared stemness program remains controversial. Here, we construct a gene module map to systematically relate transcriptional programs in embryonic stem cells (ESCs), adult tissue stem cells, and human cancers. This map reveals two predominant gene modules that distinguish ESCs and adult tissue stem cells. The ESC-like transcriptional program is activated in diverse human epithelial cancers and strongly predicts metastasis and death. c-Myc, but not other oncogenes, is sufficient to reactivate the ESC-like program in normal and cancer cells. In primary human keratinocytes transformed by Ras and IκBα, c-Myc increases the fraction of tumor-initiating cells by 150-fold, enabling tumor formation and serial propagation with as few as 500 cells. c-Myc-enhanced tumor initiation is cell-autonomous and independent of genomic instability. Thus, activation of an ESC-like transcriptional program in differentiated adult cells may induce pathologic self-renewal characteristic of cancer stem cells.
