Novel insights in the regulation of intercalated cell differentiation.

Purpose of review: Kidney intercalated cells play critical roles in regulating body acid-base balance. We recently discovered Foxp1 and two downstream transcriptional factors Dmrt2 and Hmx2 are essential for intercalated cell differentiation. This review incorporates these findings with previous reports to add insights to the molecular regulation of intercalated cell differentiation.

Recent findings: We reviewed the current understanding of intercalated cell differentiation and plasticity, and the contribution of single-cell sequencing to point to the existence of transitional cells during principal cell and intercalated cell differentiation or trans-differentiation. For molecular regulation of cell differentiation, we discuss how Notch and Foxi1 regulate principal cell/intercalated cell switch and intercalated cell differentiation, and the new finding of Foxp1 and downstream transcriptional factors in intercalated cell subtype specification.

Summary: The differentiation and balance of principal cell and intercalated cell subtypes are the foundation for maintaining acid-base balance. A clear understanding of the cellular and molecular controls of these processes provides the basis for designing intervention approaches for metabolism acidosis or alkalosis and other related diseases.