Identification and implication of tissue-enriched ligands in epithelial–endothelial crosstalk during pancreas development

Manon Moulis; Steve Vincent Maurice Runser; Laura Glorieux; Nicolas Dauguet; Christophe Vanderaa; Laurent Gatto; Donatienne Tyteca; Patrick Henriet; Francesca M. Spagnoli; Dagmar Iber; Christophe E. Pierreux

doi:10.1038/s41598-022-16072-y

Identification and implication of tissue-enriched ligands in epithelial–endothelial crosstalk during pancreas development

Manon Moulis, Steve Vincent Maurice Runser, Laura Glorieux, Nicolas Dauguet, Christophe Vanderaa, Laurent Gatto, Donatienne Tyteca, Patrick Henriet, Francesca M. Spagnoli, Dagmar Iber, Christophe E. Pierreux^*

^*Corresponding author for this work

Centre for Stem Cells & Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. BMP7 and WNT7B, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and SEMA6D, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced BMP7 limited development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of BMP7 in the intercellular communications contributing to vessel development and organization during pancreas organogenesis.

Original language	English
Article number	12498
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-16072-y
Publication status	Published - Dec 2022

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@article{d9d67cf3e8ad4c80abe35ebebc0aa856,

title = "Identification and implication of tissue-enriched ligands in epithelial–endothelial crosstalk during pancreas development",

abstract = "Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. BMP7 and WNT7B, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and SEMA6D, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced BMP7 limited development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of BMP7 in the intercellular communications contributing to vessel development and organization during pancreas organogenesis.",

author = "Manon Moulis and Runser, {Steve Vincent Maurice} and Laura Glorieux and Nicolas Dauguet and Christophe Vanderaa and Laurent Gatto and Donatienne Tyteca and Patrick Henriet and Spagnoli, {Francesca M.} and Dagmar Iber and Pierreux, {Christophe E.}",

note = "Funding Information: We (FMS, DI, CEP) acknowledge the support of the European Union{\textquoteright}s Horizon 2020 research and innovation program Pan3DP FET Open [grant Number 800981]. MM was supported by Pan3DP, LGl holds a fellowship from the Fonds pour la formation {\`a} la Recherche dans l{\textquoteright}Industrie et l{\textquoteright}Agriculture (FRIA, Belgium), CV from the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium) and DT is Research Associate form the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41598-022-16072-y",

language = "English",

volume = "12",

journal = "Scientific Reports",

issn = "2045-2322",

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T1 - Identification and implication of tissue-enriched ligands in epithelial–endothelial crosstalk during pancreas development

AU - Moulis, Manon

AU - Runser, Steve Vincent Maurice

AU - Glorieux, Laura

AU - Dauguet, Nicolas

AU - Vanderaa, Christophe

AU - Gatto, Laurent

AU - Tyteca, Donatienne

AU - Henriet, Patrick

AU - Spagnoli, Francesca M.

AU - Iber, Dagmar

AU - Pierreux, Christophe E.

N1 - Funding Information: We (FMS, DI, CEP) acknowledge the support of the European Union’s Horizon 2020 research and innovation program Pan3DP FET Open [grant Number 800981]. MM was supported by Pan3DP, LGl holds a fellowship from the Fonds pour la formation à la Recherche dans l’Industrie et l’Agriculture (FRIA, Belgium), CV from the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium) and DT is Research Associate form the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. BMP7 and WNT7B, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and SEMA6D, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced BMP7 limited development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of BMP7 in the intercellular communications contributing to vessel development and organization during pancreas organogenesis.

AB - Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. BMP7 and WNT7B, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and SEMA6D, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced BMP7 limited development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of BMP7 in the intercellular communications contributing to vessel development and organization during pancreas organogenesis.

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U2 - 10.1038/s41598-022-16072-y

DO - 10.1038/s41598-022-16072-y

M3 - Article

C2 - 35864120

AN - SCOPUS:85134571350

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 12498

ER -

Identification and implication of tissue-enriched ligands in epithelial–endothelial crosstalk during pancreas development

Abstract

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