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Optogenetic control of Wnt signaling models cell-intrinsic embryogenic patterning using 2D human pluripotent stem cell culture.
Repina, Nicole A; Johnson, Hunter J; Bao, Xiaoping; Zimmermann, Joshua A; Joy, David A; Bi, Shirley Z; Kane, Ravi S; Schaffer, David V.
Afiliação
  • Repina NA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
  • Johnson HJ; Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, CA 94720, USA.
  • Bao X; Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
  • Zimmermann JA; Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, CA 94720, USA.
  • Joy DA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
  • Bi SZ; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
  • Kane RS; Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, CA 94720, USA.
  • Schaffer DV; Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Development ; 150(14)2023 07 15.
Article em En | MEDLINE | ID: mdl-37401411
In embryonic stem cell (ESC) models for early development, spatially and temporally varying patterns of signaling and cell types emerge spontaneously. However, mechanistic insight into this dynamic self-organization is limited by a lack of methods for spatiotemporal control of signaling, and the relevance of signal dynamics and cell-to-cell variability to pattern emergence remains unknown. Here, we combine optogenetic stimulation, imaging and transcriptomic approaches to study self-organization of human ESCs (hESC) in two-dimensional (2D) culture. Morphogen dynamics were controlled via optogenetic activation of canonical Wnt/ß-catenin signaling (optoWnt), which drove broad transcriptional changes and mesendoderm differentiation at high efficiency (>99% cells). When activated within cell subpopulations, optoWnt induced cell self-organization into distinct epithelial and mesenchymal domains, mediated by changes in cell migration, an epithelial to mesenchymal-like transition and TGFß signaling. Furthermore, we demonstrate that such optogenetic control of cell subpopulations can be used to uncover signaling feedback mechanisms between neighboring cell types. These findings reveal that cell-to-cell variability in Wnt signaling is sufficient to generate tissue-scale patterning and establish a hESC model system for investigating feedback mechanisms relevant to early human embryogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes / Via de Sinalização Wnt Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes / Via de Sinalização Wnt Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article