(P-096) HAND1 Controls Epithelial Morphogenesis and Fate Specification in a Human Pluripotent Stem Cell-Based Amnion Model

Abstract Authors: Lauren N. Juga¹, Jenna C. Wettstein¹, Nikola Sekulovski¹, Amber E. Carleton¹, Anusha Rengarajan¹, Linnea E. Taniguchi¹, Jenna K. Schmidt², Thaddeus G. Golos^2,3,4, Chien-Wei Lin⁵ and Kenichiro Taniguchi^1,6

1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA
2Wisconsin National Primate Research Center (WNPRC), Madison, WI, USA

3Department of Obstetrics and Gynecology, University of Wisconsin - Madison School of Medicine, Madison, WI USA

4Department of Comparative Biosciences, University of Wisconsin - Madison School of Veterinary Medicine, Madison, WI, USA

5Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA

6Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA




Abstract Text: Amniogenesis is triggered in a collection of pluripotent epiblast cells as the human embryo implants. Previous transcriptomic analyses of stem cell-derived models of amnion showed a potential role of HAND1, a basic helix-loop-helix transcription factor, in amniogenesis, which showed dynamic expression during amnion fate specification. Strikingly, functional studies reveal a key role for HAND1 in amnion morphogenesis and lineage progression, as loss-of-function mutation of HAND1 results in impaired epithelial polarization and halted amnion fate specification. Molecularly, we identified SOX7 as a downstream target of HAND1 activity, and found that SOX7 is critical for epithelial polarization but not for amnion fate specification. Together, this study reveals a novel requirement of the HAND1-SOX7 axis in maintaining epithelial morphogenesis of developing human amnion. This work was supported by NIH grants R01-HD098231 and P51-OD011106 (to the WNPRC), as well as by MCW Start-up funds.