Increased intracellular pH is necessary for adult epithelial and embryonic stem cell differentiation.
Increased intracellular pH is necessary for adult epithelial and embryonic stem cell differentiation.
复制标题
DOI：
10.1083/jcb.201606042
复制
发表时间：
2016-11-07
期刊：
影响因子：
--
通讯作者：
Nystul TG
中科院分区：
文献类型：
--
作者：
Ulmschneider B;Grillo-Hill BK;Benitez M;Azimova DR;Barber DL;Nystul TG
Ulmschneider等人证明，在果蝇卵巢上皮干细胞和小鼠胚胎干细胞的分化期间，细胞内pH增加，阻断这种增加会损害分化，并且细胞内pH可以调节上皮干细胞中Hedgehog信号传导的强度。尽管对干细胞分化的转录调控有广泛的了解，但对动态胞质信号的作用知之甚少。我们报告说，在细胞内的pH值（pHi）的增加是必要的果蝇成年卵泡干细胞（FSC）和小鼠胚胎干细胞（mESCs）的有效分化。我们发现pHi随着FSC向卵泡前细胞（pFC）和卵泡细胞的分化而增加。果蝇Na+-H+交换剂DNhe 2的缺失降低了分化细胞中的pHi，损害了pFC分化，破坏了生殖腺形态，并降低了繁殖力。相反，增加pHi通过抑制Hedgehog途径活性促进过量pFC细胞向极/茎细胞命运分化。增加的pHi也发生在mESC分化中，并且当被阻止时，减弱幼稚细胞的自发分化，如通过microRNA簇和阶段特异性标志物的表达所确定的。我们的研究结果揭示了一个以前未被认识到的作用pHi动态分化的两种不同类型的干细胞谱系，这为理解保守的调控机制开辟了新的方向。
Ulmschneider et al. demonstrate that intracellular pH increases during differentiation of Drosophila ovarian epithelial stem cells and mouse embryonic stem cells, that blocking this increase impairs differentiation, and that intracellular pH may regulate the strength of Hedgehog signaling in epithelial stem cells. Despite extensive knowledge about the transcriptional regulation of stem cell differentiation, less is known about the role of dynamic cytosolic cues. We report that an increase in intracellular pH (pHi) is necessary for the efficient differentiation of Drosophila adult follicle stem cells (FSCs) and mouse embryonic stem cells (mESCs). We show that pHi increases with differentiation from FSCs to prefollicle cells (pFCs) and follicle cells. Loss of the Drosophila Na+–H+ exchanger DNhe2 lowers pHi in differentiating cells, impairs pFC differentiation, disrupts germarium morphology, and decreases fecundity. In contrast, increasing pHi promotes excess pFC cell differentiation toward a polar/stalk cell fate through suppressing Hedgehog pathway activity. Increased pHi also occurs with mESC differentiation and, when prevented, attenuates spontaneous differentiation of naive cells, as determined by expression of microRNA clusters and stage-specific markers. Our findings reveal a previously unrecognized role of pHi dynamics for the differentiation of two distinct types of stem cell lineages, which opens new directions for understanding conserved regulatory mechanisms.
登录
查看更多内容
影响因子：
5.6
作者：
Lee, Sang Hun;Lee, Yu Jin;Han, Ho Jae
通讯作者：
Han, Ho Jae
影响因子：
4.1
作者：
Mukherjee, Sanchita;Kallay, Laura;Rao, Rajini
通讯作者：
Rao, Rajini
影响因子：
23.9
作者：
Nystul, Todd;Spradling, Allan
通讯作者：
Spradling, Allan
DOI：
10.1083/jcb.201302131
发表时间：
2013-09-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Choi CH;Webb BA;Chimenti MS;Jacobson MP;Barber DL
通讯作者：
Barber DL
影响因子：
3.3
作者：
Nystul, Todd;Spradling, Allan
通讯作者：
Spradling, Allan