Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells

Autophagy regulates stemness Embryonic stem cells can propagate indefinitely and differentiate when called to do so. Xu et al. now analyze how cellular metabolism affects the balance between pluripotency and differentiation (see the Perspective by Borsa and Simon). For cells in the pluripotent state, the transcription factors Oct4 and Sox2 suppress chaperone-mediated autophagy (CMA). When CMA is released with differentiation, the isocitrate dehydrogenases IDH1 and IDH2 are degraded, resulting in less α-ketoglutarate, which is needed by the histone and DNA demethylases that sustain pluripotency. CMA thus links cellular metabolism to epigenetic regulation, tipping the balance between pluripotent renewal and differentiation. Science , this issue p. 397 ; see also p. 373