Analyzing embryo dormancy at single-cell resolution reveals dynamic transcriptional responses and activation of integrin-Yap/Taz prosurvival signaling

Cell Stem Cell. 2024 Sep 5;31(9):1262-1279.e8. doi: 10.1016/j.stem.2024.06.015. Epub 2024 Jul 23.

Abstract

Embryonic diapause is a reproductive adaptation that enables some mammalian species to halt the otherwise continuous pace of embryonic development. In this dormant state, the embryo exploits poorly understood regulatory mechanisms to preserve its developmental potential for prolonged periods of time. Here, using mouse embryos and single-cell RNA sequencing, we molecularly defined embryonic diapause at single-cell resolution, revealing transcriptional dynamics while the embryo seemingly resides in a state of suspended animation. Additionally, we found that the dormant pluripotent cells rely on integrin receptors to sense their microenvironment and preserve their viability via Yap/Taz-mediated prosurvival signaling.

Keywords: Taz; Yap; embryo dormancy; embryonic diapause; embryonic stem cells; epiblast; extracellular matrix; integrin; pluripotency; single-cell RNA sequencing.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Cell Survival
  • Diapause
  • Embryo, Mammalian* / metabolism
  • Embryonic Development / genetics
  • Gene Expression Regulation, Developmental
  • Integrins* / metabolism
  • Mice
  • Signal Transduction*
  • Single-Cell Analysis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • YAP-Signaling Proteins* / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Integrins
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Wwtr1 protein, mouse
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • tafazzin protein, mouse