每時(shí)每刻,人體內(nèi)成千上萬的細(xì)胞在不停的移動(dòng),尤其是免疫反應(yīng)、創(chuàng)傷修復(fù)等過程中。細(xì)胞遷移過程發(fā)生錯(cuò)誤可造成腫瘤的形成和癌細(xì)胞的擴(kuò)散。最近加州理工學(xué)院的研究人員利用線蟲對細(xì)胞遷移的過程進(jìn)行了深入研究,相關(guān)論文發(fā)表在PNAS上。
文章的通訊作者Paul Sternberg教授說,我們知道如何找到原發(fā)腫瘤,知道癌細(xì)胞何時(shí)擴(kuò)散,但卻對細(xì)胞何時(shí)遷移不清楚。Sternberg已對秀麗隱桿線蟲(Caenorhabditis elegans)進(jìn)行過多年的研究,盡管秀麗隱桿線蟲的體型很小,卻與人類有著很多相同的基因。
共同作者M(jìn)ihoko Kato說,細(xì)胞遷移是一個(gè)非常保守的過程,因此無論發(fā)生在線蟲或哺乳動(dòng)物還是人中,我們都認(rèn)為參與此過程的是一群相同的基因。
人或線蟲的細(xì)胞中都有成千上萬個(gè)基因,每個(gè)基因都有特定的功能,它們中約1/3比較活躍。為找到在細(xì)胞遷移過程中表達(dá)的基因,研究者以線蟲體內(nèi)一種名叫l(wèi)inker cell (LC)的細(xì)胞為研究對象,因?yàn)樵诰€蟲發(fā)育過程中,LC細(xì)胞的遷移基本跨越了整個(gè)線蟲的長度。
利用高性能的顯微鏡,在相隔12小時(shí)的兩個(gè)時(shí)間點(diǎn),研究者觀察并分離了幼蟲的LC細(xì)胞,而后根據(jù)測序結(jié)果和計(jì)算分析找出在這兩個(gè)遷移時(shí)間點(diǎn)高表達(dá)的基因。這種方法叫做transc**tional profiling,優(yōu)點(diǎn)是可以使用任何細(xì)胞。
研究人員選擇線蟲和人共有的基因,如果發(fā)現(xiàn)某個(gè)基因在線蟲細(xì)胞遷移中發(fā)揮作用,那么可以認(rèn)為它在人體中也有助細(xì)胞遷移。
對細(xì)胞遷移進(jìn)行深入研究有助于開發(fā)阻止這一過程的特定基因靶向的藥物。進(jìn)一步的研究中,研究人員希望找到遷移細(xì)胞的分子標(biāo)記,進(jìn)而為診斷提供便利。這項(xiàng)工作為找到癌細(xì)胞擴(kuò)散的分子機(jī)制奠定了基礎(chǔ)。
編譯自:New insight into complexities of cell migration
Functional transc**tomics of a migrating cell in Caenorhabditis elegans
Erich M. Schwarza,b,1, Mihoko Katoa,b,1, and Paul W. Sternberg
In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transc**tomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi–treated L4 larvae. We observed expression of 8,000–10,000 genes in the linker cell, 22–25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67–dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.
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