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Intracellular pH dynamics regulates intestinal stem cell lineage specification
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Journal Article
Intracellular pH dynamics regulates intestinal stem cell lineage specification
2023
Overview
Intracellular pH dynamics is increasingly recognized to regulate myriad cell behaviors. We report a finding that intracellular pH dynamics also regulates adult stem cell lineage specification. We identify an intracellular pH gradient in mouse small intestinal crypts, lowest in crypt stem cells and increasing along the crypt column. Disrupting this gradient by inhibiting H
+
efflux by Na
+
/H
+
exchanger 1 abolishes crypt budding and blocks differentiation of Paneth cells, which are rescued with exogenous WNT. Using single-cell RNA sequencing and lineage tracing we demonstrate that intracellular pH dynamics acts downstream of ATOH1, with increased pH promoting differentiation toward the secretory lineage. Our findings indicate that an increase in pH is required for the lineage specification that contributes to crypt maintenance, establishing a role for intracellular pH dynamics in cell fate decisions within an adult stem cell lineage.
Myriad extracellular and intracellular cues regulate stem cell fate choice. Here, Liu
et al
. report intracellular pH dynamics as a previously unrecognized regulator to selectively mediate the secretory cell fate decision of the intestinal stem cell.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
