Format

Send to

Choose Destination
J Cell Biol. 2016 Nov 7;215(3):345-355.

Increased intracellular pH is necessary for adult epithelial and embryonic stem cell differentiation.

Author information

1
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143.
2
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143.
3
Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143.
4
Department of Biological Sciences, San Jose State University, San Jose, CA 95192.
5
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143 todd.nystul@ucsf.edu.

Abstract

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.

PMID:
27821494
PMCID:
PMC5100294
DOI:
10.1083/jcb.201606042
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center