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

Cell Stem Cell

Institute of Molecular Medicine, National Biomedical Imaging Center, College of Future Technology, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address:

Published: August 2023

AI Article Synopsis

  • The study investigates the role of mechanical forces in the development of the mouse blastocyst, specifically how these forces affect the formation of the inner cell mass (ICM) and trophectoderm (TE).
  • Researchers use advanced live imaging techniques and experiments to measure fluid flow forces within the blastocyst and identify Klf2 as a key reporter for these forces that influence cell fate decisions.
  • Findings suggest that higher fluid flow forces lead to blastomeres becoming ICM cells, and the study provides a method for continuously monitoring these forces and their impact on cell lineage during development.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.stem.2023.07.003DOI Listing

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