Stem cell fate choices are regulated through antagonistic control of lysosomes by MYC and TFEB [RNA-Seq 3]

We show that lysosomes are antagonistically controlled by TFEB and MYC to balance catabolic and anabolic processes required for activating LT-HSC and guiding their lineage fate. TFEB-mediated induction of the endolysosomal pathway for membrane receptor degradation limits LT-HSC metabolic and mitogenic activation; this promotes quiescence and self-renewal and governs erythroid-myeloid commitment. By contrast, MYC engages biosynthetic processes while repressing lysosomal catabolism to drive LT-HSC activation. Collectively, our study identifies lysosomes as a central regulatory hub for proper and coordinated stem cell fate determination. Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentivirus to overexpress GP91 (CTRL) or TFEB. Three days later, BFP+ transduced cells were sorted for RNA extraction and sequencing. Authors state that raw data will be uploaded to the EGA database.