1. Loss of TJP1 disrupts gastrulation patterning and increases differentiation toward the germ cell lineage in human pluripotent stem cells.
- Author
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Vasic I, Libby ARG, Maslan A, Bulger EA, Zalazar D, Krakora Compagno MZ, Streets A, Tomoda K, Yamanaka S, and McDevitt TC
- Subjects
- Humans, Cell Lineage, Cell Differentiation, Germ Cells, Zonula Occludens-1 Protein genetics, Zonula Occludens-1 Protein metabolism, Gastrulation physiology, Pluripotent Stem Cells
- Abstract
Biological patterning events that occur early in development establish proper tissue morphogenesis. Identifying the mechanisms that guide these patterning events is necessary in order to understand the molecular drivers of development and disease and to build tissues in vitro. In this study, we use an in vitro model of gastrulation to study the role of tight junctions and apical/basolateral polarity in modulating bone morphogenic protein-4 (BMP4) signaling and gastrulation-associated patterning in colonies of human pluripotent stem cells (hPSCs). Disrupting tight junctions via knockdown (KD) of the scaffolding tight junction protein-1 (TJP1, also known as ZO1) allows BMP4 to robustly and ubiquitously activate pSMAD1/5 signaling over time, resulting in loss of the patterning phenotype and marked differentiation bias of pluripotent stem cells to primordial germ cell-like cells (PGCLCs). These findings give important insights into how signaling events are regulated and lead to spatial emergence of diverse cell types in vitro., Competing Interests: Declaration of interests I.V. is the founder and Chief Executive Officer of Vitra Labs, Inc. K.T. is on the scientific advisory board of I Peace, Inc., without salary. S.Y. is a scientific advisor to iPS Academia Japan, Orizuru Therapeutics, and Altos Labs without salary. T.C.M. is Vice President of Cell Engineering at SanaX. I.V. and T.C.M. are inventors on a patent filing by the Gladstone Institutes and the University of California, San Francisco, relating to high-throughput generation of primordial germ cell-like cells (PGCLCs)., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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