Developmental biology. Orienting stem cells.
Developmental biology. Orienting stem cells.
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发育生物学。
DOI：
10.1126/science.1090070
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Matunis,Erika
中科院分区：
文献类型：
--
作者：
Wallenfang,MatthewR;Matunis,Erika
干细胞的研究对于加深我们对胚胎发育、成人衰老和肿瘤形成等过程的理解具有巨大的希望。这是由于它们具有非凡的自我更新能力、产生更多干细胞以及分化成一种或多种特殊细胞类型的能力。最近的许多研究并没有关注干细胞本身，而是关注它们周围的细胞及其细胞外环境。现在认为，对于大多数干细胞类型来说，这种环境或“生态位”为干细胞继续自我更新提供了必要的信号，并且在退出该生态位后，它们开始分化 (1)。因此，干细胞决定留在生态位或离开生态位的机制应该是干细胞自我更新和分化之间平衡作用的主要参与者。在本期第 1547 页，Yamashita 等人 (2) 在果蝇睾丸的生殖干细胞生态位中探索了这一机制。他们发现干细胞本身通过定向其分裂平面来直接控制这一过程。令人惊讶的是，这种方向是通过一种明显新的不对称细胞分裂方法建立的，该方法有可能用于外部信号决定细胞命运的其他系统。果蝇睾丸平均含有九个种系干细胞，围绕着一小群不可分裂的体细胞，称为中枢（见图）。最近的两项研究表明，该中枢通过分泌生殖系干细胞自我更新所需的信号来负责创建生殖系干细胞生态位。靠近中枢的干细胞接收高水平的该信号，从而被指示进行自我更新，而较远的细胞接收较少的信号并开始分化为精原细胞 (3, 4)。 Yamashita 等人使用标有绿色荧光蛋白的微管蛋白来标记分裂细胞中的有丝分裂纺锤体。发现生殖干细胞的分裂总是垂直于中枢，因此只有一个子细胞接触中枢，而另一个子细胞则从生态位中移出（见图）。值得注意的是，其定位
The study of stem cells holds immense promise for furthering our understanding of processes such as embryonic development, adult aging, and tumor formation. This is due to their remarkable ability to self-renew, to produce more stem cells and to differentiate into one or more specialized cell types. Many recent studies have focused not on the stem cells themselves, but on the cells surrounding them and their extracellular environment. It is now thought that for most stem cell types this environment, or “niche,” provides signals necessary for the stem cells to continue to self-renew, and that upon exit from this niche they begin to undergo differentiation (1). Thus, the mechanism by which stem cells decide either to remain in the niche or to leave it should be a major player in the balancing act between stem cell self-renewal and differentiation. On page 1547 of this issue, Yamashita et al.(2) explore this mechanism in the germline stem cell niche of the Drosophila testis. They find that the stem cells themselves control this process directly by orienting the plane of their division. Surprisingly, this orientation is established by an apparently new method of asymmetric cell division, which could potentially be used in other systems where external signals dictate cell fate. The Drosophila testis contains an average of nine germline stem cells surrounding a small cluster of nondividing somatic cells known as the hub (see the figure). Two recent studies have shown that the hub is responsible for creating the germline stem cell niche by secreting a signal that is required by germline stem cells for their selfrenewal. Stem cells next to the hub receive high levels of this signal and are thus instructed to self-renew, whereas cells further away receive less signal and begin to differentiate into spermatogonia (3, 4). Using tubulin tagged with green fluorescent protein, which marks the mitotic spindle in dividing cells, Yamashita et al. find that germline stem cells always orient their divisions perpendicular to the hub, so that only one daughter cell contacts the hub, whereas the other is displaced from the niche (see the figure). Remarkably, the positioning of