Genetic reporter for live tracing fluid flow forces during cell fate segregation in mouse blastocyst development

• Published in: Cell stem cell Vol. 30; no. 8; pp. 1110 - 1123.e9
• Main Authors: Zhang, Youdong, Li, Xin, Gao, Shu, Liao, Yuanhui, Luo, Yingjie, Liu, Min, Bian, Yunkun, Xiong, Haiqing, Yue, Yanzhu, He, Aibin
• Format: Journal Article
• Language: English
• Published: United States 03.08.2023
• Subjects: live imaging; blastocyst; cell fate control; mechanical forces
• ISSN: 1934-5909; 1875-9777; 1875-9777
• DOI: 10.1016/j.stem.2023.07.003

Mechanical forces are known to be important in mammalian blastocyst formation; however, due to limited tools, specific force inputs and how they relay to first cell fate control of inner cell mass (ICM) and/or trophectoderm (TE) remain elusive. Combining in toto live imaging and various perturbation experiments, we demonstrate and measure fluid flow forces existing in the mouse blastocyst cavity and identify Klf2(Krüppel-like factor 2) as a fluid force reporter with force-responsive enhancers. Long-term live imaging and lineage reconstructions reveal that blastomeres subject to higher fluid flow forces adopt ICM cell fates. These are reinforced by internal ferrofluid-induced flow force assays. We also utilize ex vivo fluid flow force mimicking and pharmacological perturbations to confirm mechanosensing specificity. Together, we report a genetically encoded reporter for continuously monitoring fluid flow forces and cell fate decisions and provide a live imaging framework to infer force information enriched lineage landscape during development. VIDEO ABSTRACT.