Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Development. 2011 Aug;138(16):3367-76. doi: 10.1242/dev.065797. Epub 2011 Jul 13.
Adult stem cells modulate their output by varying between symmetric and asymmetric divisions, but have rarely been observed in living intact tissues. Germline stem cells (GSCs) in the Drosophila testis are anchored to somatic hub cells and were thought to exclusively undergo oriented asymmetric divisions, producing one stem cell that remains hub-anchored and one daughter cell displaced out of the stem cell-maintaining micro-environment (niche). We developed extended live imaging of the Drosophila testis niche, allowing us to track individual germline cells. Surprisingly, new wild-type GSCs are generated in the niche during steady-state tissue maintenance by a previously undetected event we term 'symmetric renewal', where interconnected GSC-daughter cell pairs swivel such that both cells contact the hub. We also captured GSCs undergoing direct differentiation by detaching from the hub. Following starvation-induced GSC loss, GSC numbers are restored by symmetric renewals. Furthermore, upon more severe (genetically induced) GSC loss, both symmetric renewal and de-differentiation (where interconnected spermatogonia fragment into pairs while moving towards then establishing contact with the hub) occur simultaneously to replenish the GSC pool. Thus, stereotypically oriented stem cell divisions are not always correlated with an asymmetric outcome in cell fate, and changes in stem cell output are governed by altered signals in response to tissue requirements.
成体干细胞通过对称分裂和不对称分裂之间的变化来调节其输出，但在活体完整组织中很少被观察到。果蝇睾丸中的生殖干细胞（GSCs）附着在体细胞枢纽细胞上，被认为仅进行定向不对称分裂，产生一个仍然与枢纽锚定的干细胞和一个离开维持干细胞的微环境（龛）的子细胞。我们开发了对果蝇睾丸龛的扩展活体成像，使我们能够跟踪单个生殖细胞。令人惊讶的是，在稳态组织维持期间，通过我们称之为“对称更新”的以前未检测到的事件，在龛中产生新的野生型 GSCs，其中相互连接的 GSC-子细胞对旋转，使得两个细胞都与枢纽接触。我们还通过从枢纽上分离来捕获正在进行直接分化的 GSCs。在饥饿诱导的 GSC 损失后，通过对称更新来恢复 GSC 数量。此外，在更严重的（遗传诱导的）GSC 损失后，对称更新和去分化（相互连接的精原细胞片段成对，同时向枢纽移动并与之建立接触）同时发生，以补充 GSC 池。因此，典型定向的干细胞分裂并不总是与细胞命运的不对称结果相关，并且干细胞输出的变化受组织需求响应的改变信号的控制。
