Arp2/3 complex activity is necessary for mouse ESC differentiation, times formative pluripotency, and enables lineage specification
Year: 2022
Type: article
Abstract: Mouse embryonic stem cells (mESCs), a model for differentiation into primed epiblast-like cells (EpiLCs), have revealed transcriptional and epigenetic control of early embryonic development. The control and significance of morphological changes, however, remain less defined. We show marked changes in morphology and actin architectures during differentiation that depend on Arp2/3 complex but not formin activity. Inhibiting Arp2/3 complex activity pharmacologically or genetically does not block exit from naive pluripotency, but attenuates increases in EpiLC markers. We find that inhibiting Arp2/3 complex activity delays formative pluripotency and causes globally defective lineage specification as indicated by RNA sequencing, with significant effects on TBX3-depedendent transcriptional programs. We also identify two previously unreported indicators of mESC differentiation, namely, MRTF and FHL2, which have inverse Arp2/3 complex-dependent nuclear translocation. Our findings on Arp2/3 complex activity in differentiation and the established role of formins in EMT indicate that these two actin nucleators regulate distinct modes of epithelial plasticity.
Source: Stem Cell Reports
Authors: Francesca M. Aloisio, Diane L. Barber
Institution: University of California, San Francisco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: National Science Foundation, Foundation for the National Institutes of Health, Howard Hughes Medical Institute, National Institutes of Health, Directorate for Biological Sciences, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources
OpenAlex ID: W4281864888