Disruption of Epithelial Integrity Drives Mesendoderm Differentiation in Human Induced Pluripotent Stem Cells by Enabling BMP and ACTIVIN Sensing Article Swipe
Diane Rattier
,
Thomas Legier
,
Thomas Vannier
,
Flavio Maina
,
Rosanna Dono
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.10.22.465459
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.10.22.465459
The processes of primitive streak formation and fate specification in the mammalian epiblast rely on complex interactions between morphogens and tissue organization. Little is known about how these instructive cues functionally interact to regulate gastrulation. We interrogated the interplay between tissue organization and morphogens by using human induced pluripotent stem cells (hiPSCs) down-regulated for the morphogen regulator GLYPICAN-4, in which defects in tight junctions result in areas of disrupted epithelial integrity. Remarkably, this phenotype does not affect hiPSC stemness, but impacts on cell fate acquisition processes. Strikingly, cells within disrupted areas become competent to perceive BMP4 and ACTIVIN A/NODAL gastrulation signals and thus, differentiate into mesendoderm. Yet, disruption of epithelial integrity prolongs temporal activation of BMP4 and ACTIVIN A/NODAL downstream effectors and correlates with enhanced hiPSC endoderm/mesoderm differentiation potential. Altogether, our results disclose epithelial cell integrity as a key determinant of TGF- β activity and highlight a new mechanism guiding morphogen sensing and spatial cell fate change within an epithelium.
Related Topics
Concepts
Morphogen
Gastrulation
Cell biology
Epiblast
Mesoderm
Primitive streak
Nodal signaling
Cell fate determination
Biology
Induced pluripotent stem cell
NODAL
Endoderm
Stem cell
Cellular differentiation
Embryonic stem cell
Anatomy
Embryo
Embryogenesis
Genetics
Transcription factor
Gene
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.10.22.465459
- https://www.biorxiv.org/content/biorxiv/early/2021/10/23/2021.10.22.465459.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3208496920
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3208496920Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.10.22.465459Digital Object Identifier
- Title
-
Disruption of Epithelial Integrity Drives Mesendoderm Differentiation in Human Induced Pluripotent Stem Cells by Enabling BMP and ACTIVIN SensingWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-10-23Full publication date if available
- Authors
-
Diane Rattier, Thomas Legier, Thomas Vannier, Flavio Maina, Rosanna DonoList of authors in order
- Landing page
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https://doi.org/10.1101/2021.10.22.465459Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/10/23/2021.10.22.465459.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2021/10/23/2021.10.22.465459.full.pdfDirect OA link when available
- Concepts
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Morphogen, Gastrulation, Cell biology, Epiblast, Mesoderm, Primitive streak, Nodal signaling, Cell fate determination, Biology, Induced pluripotent stem cell, NODAL, Endoderm, Stem cell, Cellular differentiation, Embryonic stem cell, Anatomy, Embryo, Embryogenesis, Genetics, Transcription factor, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2022: 1Per-year citation counts (last 5 years)
- References (count)
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53Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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