First Author | Zhang Y | Year | 2023 |
Journal | Cell Stem Cell | Volume | 30 |
Issue | 8 | Pages | 1110-1123.e9 |
PubMed ID | 37541214 | Mgi Jnum | J:354831 |
Mgi Id | MGI:7518145 | Doi | 10.1016/j.stem.2023.07.003 |
Citation | Zhang Y, et al. (2023) Genetic reporter for live tracing fluid flow forces during cell fate segregation in mouse blastocyst development. Cell Stem Cell 30(8):1110-1123.e9 |
abstractText | 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(Kruppel-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. |