Bioelectric regulation of stem cell fate: From the plasma membrane to organelles.

Stem cell identity has traditionally been viewed through the lens of transcriptional and metabolic programs. Recent work has revealed an additional layer of complexity: the plasma membrane and intracellular organelles maintain compartment-specific membrane potentials, pH gradients, and ion dynamics that can influence stemness and fate. In this review, we synthesize recent advances identified across diverse stem cell populations to highlight convergent and divergent bioelectric mechanisms driving cell fate decisions. We explore how plasma membrane mechanosensors convert physical cues into internal ionic signals. We next examine the influence of lysosomal pH on metabolic programming to support cell transitions. We then discuss how differences in mitochondrial membrane potentials (MMPs) and inheritance, endoplasmic reticulum (ER)-calcium handling, and ER-mitochondrial coupling influence lineage commitment. Finally, we consider how nuclear ionic and mechano-osmotic conditions may shape chromatin organization and transcriptional competence. Collectively, these studies position the plasma membrane and organelles as coupled nodes within an integrated bioelectric network. This emerging framework identifies new questions about how compartment-specific ionic states are coordinated and suggests potential strategies for therapeutically redirecting cell fate.