Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3

Villegas et al. identify mouse embryonic stem cell differentiation drivers in a genome-wide CRISPR/Cas9 screen. The majority of these are part of a lysosomal signaling pathway that licenses differentiation by inactivating the transcription factor Tfe3. The authors discover lysosomal-signaling-insensitive Tfe3 mutations as potentially causal for a human developmental disorder.

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