%0 Video-Audio Media %T Genetic reporter for live tracing fluid flow forces during cell fate segregation in mouse blastocyst development. %A Zhang Y %A Li X %A Gao S %A Liao Y %A Luo Y %A Liu M %A Bian Y %A Xiong H %A Yue Y %A He A %J Cell Stem Cell %V 30 %N 8 %D 2023 08 3 %M 37541214 %F 25.269 %R 10.1016/j.stem.2023.07.003 %X 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.