Stem cells require high amounts of energy to replicate their genome and organelles and differentiate into numerous cell types. Therefore, metabolic stress has a major impact on stem cell fate determination, including self-renewal, quiescence, and differentiation. Lysosomes are catabolic organelles that influence stem cell function and fate by regulating the degradation of intracellular components and maintaining cellular homeostasis in response to metabolic stress. Lysosomal functions altered by metabolic stress are tightly regulated by the transcription factor EB (TFEB) and TFE3, critical regulators of lysosomal gene expression. Therefore, understanding the regulatory mechanism of TFEB-mediated lysosomal function may provide some insight into stem cell fate determination under metabolic stress. In this review, we summarize the molecular mechanism of TFEB/TFE3 in modulating stem cell lysosomal function and then elucidate the role of TFEB/TFE3-mediated transcriptional activity in the determination of stem cell fate under metabolic stress.
Keywords: lysosomal function; metabolic stress; stem cell fate; transcription factor EB.