每時(shí)每刻，人體內(nèi)成千上萬(wàn)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(guò)程中。細(xì)胞遷移過(guò)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(chóng)對(duì)細(xì)胞遷移的過(guò)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(shuō)，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(duì)細(xì)胞何時(shí)遷移不清楚。Sternberg已對(duì)秀麗隱桿線蟲(chóng)（Caenorhabditis elegans）進(jìn)行過(guò)多年的研究，盡管秀麗隱桿線蟲(chóng)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(shuō)，細(xì)胞遷移是一個(gè)非常保守的過(guò)程，因此無(wú)論發(fā)生在線蟲(chóng)或哺乳動(dòng)物還是人中，我們都認(rèn)為參與此過(guò)程的是一群相同的基因。

    人或線蟲(chóng)的細(xì)胞中都有成千上萬(wàn)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(guò)程中表達(dá)的基因，研究者以線蟲(chóng)體內(nèi)一種名叫l(wèi)inker cell （LC）的細(xì)胞為研究對(duì)象，因?yàn)樵诰€蟲(chóng)發(fā)育過(guò)程中，LC細(xì)胞的遷移基本跨越了整個(gè)線蟲(chóng)的長(zhǎng)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(chóng)的LC細(xì)胞，而后根據(jù)測(cè)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(chóng)和人共有的基因，如果發(fā)現(xiàn)某個(gè)基因在線蟲(chóng)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(duì)細(xì)胞遷移進(jìn)行深入研究有助于開(kāi)發(fā)阻止這一過(guò)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.