Mechanical imbalance between normal and transformed cells drives epithelial homeostasis through cell competition

Published: Jan. 2, 2025

Cell competition in epithelial tissue eliminates transformed cells expressing activated oncoproteins to maintain homeostasis. Although the process is now understood be of mechanochemical origin, direct mechanical characterization and associated biochemical underpinnings are lacking. Here, we employ tissue-scale stress compressibility measurements theoretical modeling unveil a imbalance between normal cells, which drives cell competition. In mouse intestinal epithelium monolayer, get compacted during Stress microscopy reveals an emergent compressive at loci leading this compaction. A cell-based self-propelled Voronoi model predicts that originates from difference collective competing populations. new measurement technique named gel compression then elucidates two-fold higher population than population. Mechanistically, weakened cell-cell adhesions due reduced junctional abundance E-cadherin render them collectively more compressible cells. Taken together, our findings basis for homeostasis against oncogenic transformations with implications defense cancer.

Language: Английский

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Mechanical imbalance between normal and transformed cells drives epithelial homeostasis through cell competition

Published: Jan. 2, 2025

Cell competition in epithelial tissue eliminates transformed cells expressing activated oncoproteins to maintain homeostasis. Although the process is now understood be of mechanochemical origin, direct mechanical characterization and associated biochemical underpinnings are lacking. Here, we employ tissue-scale stress compressibility measurements theoretical modeling unveil a imbalance between normal cells, which drives cell competition. In mouse intestinal epithelium monolayer, get compacted during Stress microscopy reveals an emergent compressive at loci leading this compaction. A cell-based self-propelled Voronoi model predicts that originates from difference collective competing populations. new measurement technique named gel compression then elucidates two-fold higher population than population. Mechanistically, weakened cell-cell adhesions due reduced junctional abundance E-cadherin render them collectively more compressible cells. Taken together, our findings basis for homeostasis against oncogenic transformations with implications defense cancer.

Language: Английский

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Epithelial apoptosis: A back-and-forth mechanical interplay between the dying cell and its surroundings

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 168, P. 1 - 12

Published: Feb. 21, 2025

Language: Английский

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Epithelial cell extrusion at a glance

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(8)

Published: April 15, 2025

ABSTRACT The robustness and plasticity of epithelial tissues rely on the capacity such to eliminate cells without affecting their sealing. This is achieved by cell extrusion – a well-orchestrated series remodelling steps involving eliminated its neighbours which ensures constant maintenance mechanical chemical barrier properties while allowing expulsion. In this Cell Science at Glance accompanying poster, we describe that take place within dying or extruding cells, as well neighbouring outlining commonalities variations between organisms. These include reorganization cytoskeleton cell–cell junctions alters contribution coupling mechanotransduction. We also discuss larger-scale coordination tissue morphogenesis, surveillance mechanisms, pathologies cancer chronic inflammation. Altogether, outline complexity minimalist morphogenetic process.

Language: Английский

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Interacting Fat1 and Dchs Planar Cell Polarity Proteins Supported by Fjx1 Serve as Heterodimeric Intercellular Bridges Crucial to Support Spermatogenesis

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 355 - 374

Published: Jan. 1, 2025

Language: Английский

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Tuning apicobasal polarity and junctional recycling in the hemogenic endothelium orchestrates the morphodynamic complexity of emerging pre-hematopoietic stem cells

eLife, Journal Year: 2024, Volume and Issue: 12

Published: May 29, 2024

Hematopoietic stem cells emerge in the embryo from an aortic-derived tissue called hemogenic endothelium (HE). The HE appears to give birth of different nature and fate but molecular principles underlying this complexity are largely unknown. Here we show, zebrafish embryo, that two cell types aortic floor with radically morphodynamics. With support live imaging, bring evidence suggesting mechanics emergence rely, or not, on apicobasal polarity establishment. While first type is characterized by reinforcement maintenance apical/luminal membrane until release, second emerges via a dynamic process reminiscent trans-endothelial migration. Interfering Runx1 function suggests balance between depends tuning at level HE. In unexpectedly, show Pard3ba – one four Pard3 proteins expressed sensitive interference activity, endothelial cells. This supports idea signaling cross talk controlling its associated features, addition, using new transgenic fish lines express Junctional Adhesion Molecules functional interference, for essential role ArhGEF11/PDZ-RhoGEF HE-endothelial interface, including cell-cell intercalation, which ultimately required completion. Overall, highlight critical cellular events endothelial-to-hematopoietic transition complexity, potential impact fate.

Language: Английский

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Mechanical imbalance between normal and transformed cells drives epithelial homeostasis through cell competition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 29, 2023

Abstract Cell competition in epithelial tissue eliminates transformed cells expressing activated oncoproteins to maintain homeostasis. Although the process is now understood be of mechanochemical origin, direct mechanical characterization and associated biochemical underpinnings are lacking. Here, we employ tissue-scale stress compressibility measurements theoretical modeling unveil a imbalance between normal cells, which drives cell competition. In mouse intestinal epithelium monolayer, get compacted during Stress microscopy reveals an emergent compressive at loci leading this compaction. A cell-based self-propelled Voronoi model predicts that originates from difference collective competing populations. new measurement technique named gel compression then elucidates two-fold higher population than population. Mechanistically, weakened cell-cell adhesions due reduced junctional abundance E-cadherin render them collectively more compressible cells. Taken together, our findings basis for homeostasis against oncogenic transformations with implications defense cancer.

Language: Английский

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Tuning apicobasal polarity and junctional recycling in the hemogenic endothelium orchestrates the morphodynamic complexity of emerging pre-hematopoietic stem cells

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Nov. 3, 2023

Hematopoietic stem cells emerge in the embryo from an aortic-derived tissue called hemogenic endothelium (HE). The HE appears to give birth of different nature and fate but molecular principles underlying this complexity are largely unknown. Here we show, zebrafish embryo, that two cell types aortic floor with radically morphodynamics. With support live imaging, bring evidence suggesting mechanics emergence rely, or not, on apicobasal polarity establishment. While first type is characterized by reinforcement maintenance apical/luminal membrane until release, second emerges via a dynamic process reminiscent trans-endothelial migration. Interfering Runx1 function suggests balance between depends tuning at level HE. In unexpectedly, show Pard3ba - one four Pard3 proteins expressed sensitive interference activity, endothelial cells. This supports idea signaling cross talk controlling its associated features, addition, using new transgenic fish lines express Junctional Adhesion Molecules functional interference, for essential role ArhGEF11/PDZ-RhoGEF HE-endothelial interface, including cell-cell intercalation, which ultimately required completion. Overall, highlight critical cellular events endothelial-to-hematopoietic transition complexity, potential impact fate.

Language: Английский

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Tuning apicobasal polarity and junctional recycling in the hemogenic endothelium orchestrates the morphodynamic complexity of emerging pre-hematopoietic stem cells

Published: April 11, 2024

Hematopoietic stem cells emerge in the embryo from an aortic-derived tissue called hemogenic endothelium (HE). The HE appears to give birth of different nature and fate but molecular principles underlying this complexity are largely unknown. Here we show, zebrafish embryo, that two cell types aortic floor with radically morphodynamics. With support live imaging, bring evidence suggesting mechanics emergence rely, or not, on apicobasal polarity establishment. While first type is characterized by reinforcement maintenance apical/luminal membrane until release, second emerges via a dynamic process reminiscent trans-endothelial migration. Interfering Runx1 function suggests balance between depends tuning at level HE. In unexpectedly, show Pard3 isoform - Pard3ba sensitive interference activity, endothelial cells. This supports idea signaling cross talk controlling its associated features, addition, using new transgenic fish lines express Junctional Adhesion Molecules functional interference, for essential role ArhGEF11/PDZ-RhoGEF HE-endothelial interface, including cell-cell intercalation, which ultimately required completion. Overall, highlight critical cellular events endothelial-to-hematopoietic transition complexity, potential impact fate.

Language: Английский

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Tuning apicobasal polarity and junctional recycling in the hemogenic endothelium orchestrates the morphodynamic complexity of emerging pre-hematopoietic stem cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 3, 2023

Abstract Hematopoietic stem cells emerge in the embryo from an aortic-derived tissue called hemogenic endothelium (HE). The HE appears to give birth of different nature and fate but molecular principles underlying this complexity are largely unknown. Here we show, zebrafish embryo, that two cell types aortic floor with radically morphodynamics. With support live imaging, bring evidence suggesting mechanics emergence rely, or not, on apicobasal polarity establishment. While first type is characterized by reinforcement maintenance apical/luminal membrane until release, second emerges via a dynamic process reminiscent trans-endothelial migration. Interfering Runx1 function suggests balance between depends tuning at level HE. In unexpectedly, show Pard3 isoform - Pard3ba sensitive interference activity, endothelial cells. This supports idea signaling cross talk controlling its associated features, addition, using new transgenic fish lines express Junctional Adhesion Molecules functional interference, for essential role ArhGEF11/PDZ-RhoGEF HE-endothelial interface, including cell-cell intercalation, which ultimately required completion. Overall, highlight critical cellular events endothelial-to-hematopoietic transition complexity, potential impact fate.

Language: Английский

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