Yap1 safeguards mouse embryonic stem cells from excessive apoptosis during differentiation

• DOI: 10.7554/elife.40167
• Publication Date: 2018-12-18T13:01:05Z
• Authors: Lucy LeBlanc; Bum-Kyu Lee; Andy C Yu; Mijeong Kim; Aparna V Kambhampati; Shannon M Dupont; Davide Seruggia; Byoung U Ryu; Stuart H Orkin; Jonghwan Kim
• Keywords: YAP1; Hippo signaling pathway; Cell fate determination

Approximately, 30% of embryonic stem cells (ESCs) die after exiting self-renewal, but regulators this process are not well known. Yap1 is a Hippo pathway transcriptional effector that plays numerous roles in development and cancer. However, its functions ESC differentiation remain poorly characterized. We first reveal ESCs lacking experience massive cell death upon the exit from self-renewal. subsequently show contextually protects differentiating, self-renewing, hyperactivation apoptotic cascade. Mechanistically, strongly activates anti-apoptotic genes via cis-regulatory elements while mildly suppressing pro-apoptotic genes, which moderates level mitochondrial priming occurs during differentiation. Individually modulating expression single apoptosis-related targeted by sufficient to augment or hinder survival Our demonstration context-dependent pro-survival contributes our understanding balance between fate changes.