每時每刻,人體內成千上萬的細胞在不停的移動,尤其是免疫反應、創(chuàng)傷修復等過程中。細胞遷移過程發(fā)生錯誤可造成腫瘤的形成和癌細胞的擴散。最近加州理工學院的研究人員利用線蟲對細胞遷移的過程進行了深入研究,相關論文發(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,知道癌細胞何時擴散,但卻對細胞何時遷移不清楚。Sternberg已對秀麗隱桿線蟲(Caenorhabditis elegans)進行過多年的研究,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Mihoko Kato說,細胞遷移是一個非常保守的過程,因此無論發(fā)生在線蟲或哺乳動物還是人中,我們都認為參與此過程的是一群相同的基因。
人或線蟲的細胞中都有成千上萬個基因,每個基因都有特定的功能,它們中約1/3比較活躍。為找到在細胞遷移過程中表達的基因,研究者以線蟲體內一種名叫l(wèi)inker cell (LC)的細胞為研究對象,因為在線蟲發(fā)育過程中,LC細胞的遷移基本跨越了整個線蟲的長度。
利用高性能的顯微鏡,在相隔12小時的兩個時間點,研究者觀察并分離了幼蟲的LC細胞,而后根據(jù)測序結果和計算分析找出在這兩個遷移時間點高表達的基因。這種方法叫做transc**tional profiling,優(yōu)點是可以使用任何細胞。
研究人員選擇線蟲和人共有的基因,如果發(fā)現(xiàn)某個基因在線蟲細胞遷移中發(fā)揮作用,那么可以認為它在人體中也有助細胞遷移。
對細胞遷移進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。進一步的研究中,研究人員希望找到遷移細胞的分子標記,進而為診斷提供便利。這項工作為找到癌細胞擴散的分子機制奠定了基礎。
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.