biostudies-literatureSharma KNorges ForskningsrådKreftforeningen1915-1931https://www.ebi.ac.uk/biostudies/studies/S-EPMC9450964biostudies-literatureUnknown18(8)Early events during development leading to exit from a pluripotent state and commitment toward a specific germ layer still need in-depth understanding. Autophagy has been shown to play a crucial role in both development and differentiation. This study employs human embryonic and induced pluripotent stem cells to understand the early events of lineage commitment with respect to the role of autophagy in this process. Our data indicate that a dip in autophagy facilitates exit from pluripotency. Upon exit, we demonstrate that the modulation of autophagy affects SOX2 levels and lineage commitment, with induction of autophagy promoting SOX2 degradation and mesendoderm formation, whereas inhibition of autophagy causes SOX2 accumulation and neuroectoderm formation. Thus, our results indicate that AutophagyAutophagy modulates cell fate decisions during lineage commitment.PMC9450964171318262652262613269881247624221831Baumgarten SFSullivan GJHarrison SGupta SChollet MESiller RAndersen ESimonsen AAsp NTSharma KfalseAutophagy modulates cell fate decisions during lineage commitment.Early events during development leading to exit from a pluripotent state and commitment toward a specific germ layer still need in-depth understanding. Autophagy has been shown to play a crucial role in both development and differentiation. This study employs human embryonic and induced pluripotent stem cells to understand the early events of lineage commitment with respect to the role of autophagy in this process. Our data indicate that a dip in autophagy facilitates exit from pluripotency. Upon exit, we demonstrate that the modulation of autophagy affects SOX2 levels and lineage commitment, with induction of autophagy promoting SOX2 degradation and mesendoderm formation, whereas inhibition of autophagy causes SOX2 accumulation and neuroectoderm formation. Thus, our results indicate that 2022-01-01T00:00:00Z2022 Aug2026-04-08T11:59:49.568Z2025-02-19T04:38:30.149ZS-EPMC94509643492390910.1080/15548627.2021.2008691