Intracellular PH Dynamics Regulates Intestinal Stem Cell Lineage Specification

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jun 23

PMID 37353491

Authors

Yi Liu

Efren Reyes

David Castillo-Azofeifa

Ophir D Klein

Todd Nystul

Diane L Barber

Affiliations

Soon will be listed here.

Abstract

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.

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