Live imaging of the Drosophila spermatogonial stem cell niche reveals novel mechanisms regulating germline stem cell output

Live imaging of the Drosophila spermatogonial stem cell niche reveals novel mechanisms regulating germline stem cell output
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DOI:
10.1242/dev.065797
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发表时间:
2011-08-15
期刊:
影响因子:
4.6
通讯作者:
Matunis, Erika
Matunis, Erika
中科院分区:
生物学2区
文献类型:
--
作者:
Sheng, X. Rebecca;Matunis, Erika

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成体干细胞通过在对称和不对称分裂之间变化来调节其输出,但很少在活的完整组织中观察到。果蝇睾丸中的生殖系干细胞(GSC)锚定在体细胞中枢细胞上,并被认为只进行定向不对称分裂,产生一个保持中枢锚定的干细胞和一个从维持干细胞的微环境(小生境)中移位的子细胞。我们开发了果蝇睾丸生态位的延长实时成像,使我们能够跟踪单个生殖细胞。令人惊讶的是,新的野生型GSC在稳态组织维持期间通过先前未检测到的事件在小生境中产生,我们称之为“对称更新”,其中互连的GSC-子细胞对旋转,使得两个细胞都接触枢纽。我们还通过从枢纽分离来捕获经历直接分化的GSC。饥饿引起的GSC损失后,GSC数量通过对称更新恢复。此外,在更严重的(遗传诱导的)GSC损失时,对称更新和去分化(其中相互连接的精原细胞片段成对,同时向中心移动,然后与中心建立接触)同时发生,以补充GSC池。因此,定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由响应于组织需求的改变的信号控制。
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.