Embigin is a fibronectin receptor that affects sebaceous gland differentiation and metabolism
Embigin is a fibronectin receptor that affects sebaceous gland differentiation and metabolism
Stem cell renewal and differentiation are regulated by interactions with the niche. Although multiple cell populations have been identified in distinct anatomical compartments, little is known about niche-specific molecular factors. Using skin as a model system and combining single-cell RNA-seq data analysis, immunofluorescence, and transgenic mouse models, we show that the transmembrane protein embigin is specifically expressed in the sebaceous gland and that the number of embigin-expressing cells is negatively regulated by Wnt. The loss of embigin promotes exit from the progenitor compartment and progression toward differentiation, and also compromises lipid metabolism. Embigin modulates sebaceous niche architecture by affecting extracellular matrix organization and basolateral targeting of monocarboxylate transport. We discover through ligand screening that embigin is a direct fibronectin receptor, binding to the N-terminal fibronectin domain without impairing integrin function. Our results solve the long-standing question of how embigin regulates cell adhesion and demonstrate a mechanism that couples adhesion and metabolism.
Animals, Cell Adhesion, Cell Differentiation, Fibronectins, Integrin alpha5beta1, Integrin beta1, Integrins/metabolism, Mice, Sebaceous Glands
1453-1465.e7
Sipilä, Kalle
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Rognoni, Emanuel
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Jokinen, Johanna
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Tewary, Mukul
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Vietri Rudan, Matteo
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Talvi, Salli
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Jokinen, Ville
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Dahlström, Käthe M
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Liakath-Ali, Kif
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Mobasseri, Atefeh
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Du-Harpur, Xinyi
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Käpylä, Jarmo
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Nutt, Stephen L
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Salminen, Tiina A
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Heino, Jyrki
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Watt, Fiona M
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20 June 2022
Sipilä, Kalle
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Rognoni, Emanuel
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Jokinen, Johanna
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Tewary, Mukul
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Vietri Rudan, Matteo
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Talvi, Salli
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Jokinen, Ville
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Dahlström, Käthe M
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Liakath-Ali, Kif
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Mobasseri, Atefeh
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Du-Harpur, Xinyi
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Käpylä, Jarmo
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Nutt, Stephen L
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Salminen, Tiina A
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Heino, Jyrki
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Watt, Fiona M
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Sipilä, Kalle, Rognoni, Emanuel, Jokinen, Johanna, Tewary, Mukul, Vietri Rudan, Matteo, Talvi, Salli, Jokinen, Ville, Dahlström, Käthe M, Liakath-Ali, Kif, Mobasseri, Atefeh, Du-Harpur, Xinyi, Käpylä, Jarmo, Nutt, Stephen L, Salminen, Tiina A, Heino, Jyrki and Watt, Fiona M
(2022)
Embigin is a fibronectin receptor that affects sebaceous gland differentiation and metabolism.
Developmental Cell, 57 (12), .
(doi:10.1016/j.devcel.2022.05.011).
Abstract
Stem cell renewal and differentiation are regulated by interactions with the niche. Although multiple cell populations have been identified in distinct anatomical compartments, little is known about niche-specific molecular factors. Using skin as a model system and combining single-cell RNA-seq data analysis, immunofluorescence, and transgenic mouse models, we show that the transmembrane protein embigin is specifically expressed in the sebaceous gland and that the number of embigin-expressing cells is negatively regulated by Wnt. The loss of embigin promotes exit from the progenitor compartment and progression toward differentiation, and also compromises lipid metabolism. Embigin modulates sebaceous niche architecture by affecting extracellular matrix organization and basolateral targeting of monocarboxylate transport. We discover through ligand screening that embigin is a direct fibronectin receptor, binding to the N-terminal fibronectin domain without impairing integrin function. Our results solve the long-standing question of how embigin regulates cell adhesion and demonstrate a mechanism that couples adhesion and metabolism.
Text
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More information
Accepted/In Press date: 16 May 2022
e-pub ahead of print date: 6 June 2022
Published date: 20 June 2022
Keywords:
Animals, Cell Adhesion, Cell Differentiation, Fibronectins, Integrin alpha5beta1, Integrin beta1, Integrins/metabolism, Mice, Sebaceous Glands
Identifiers
Local EPrints ID: 491419
URI: http://eprints.soton.ac.uk/id/eprint/491419
ISSN: 1534-5807
PURE UUID: 2b30243a-b66a-4912-a818-914f66bcfef1
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Date deposited: 21 Jun 2024 17:09
Last modified: 21 Aug 2025 02:49
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Contributors
Author:
Kalle Sipilä
Author:
Emanuel Rognoni
Author:
Johanna Jokinen
Author:
Mukul Tewary
Author:
Matteo Vietri Rudan
Author:
Salli Talvi
Author:
Ville Jokinen
Author:
Käthe M Dahlström
Author:
Kif Liakath-Ali
Author:
Atefeh Mobasseri
Author:
Xinyi Du-Harpur
Author:
Jarmo Käpylä
Author:
Stephen L Nutt
Author:
Tiina A Salminen
Author:
Jyrki Heino
Author:
Fiona M Watt
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