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Embigin is a fibronectin receptor that affects sebaceous gland differentiation and metabolism

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
1534-5807
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
5a03139c-2880-4c67-8c72-aee337fefe1a
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
1a615afb-2326-4387-94dd-9d37f95a205e
Rognoni, Emanuel
e180c550-fc77-434b-b0c0-2c1190a28ae7
Jokinen, Johanna
9a59f5cd-894a-46d2-a803-03bf2f385b0a
Tewary, Mukul
5469143e-2c32-490f-a319-d0026849f275
Vietri Rudan, Matteo
5a03139c-2880-4c67-8c72-aee337fefe1a
Talvi, Salli
c28011c0-9d7e-4fb4-86dd-9df2836de170
Jokinen, Ville
4316d1b1-c928-42ce-93d4-d7edce07c34e
Dahlström, Käthe M
58f2c21a-16a9-4a4a-8398-8aa5cc79de8b
Liakath-Ali, Kif
8d5a020c-e976-4901-9195-68f4bc0de74e
Mobasseri, Atefeh
610aead9-e410-4cbe-b387-8d01f0ffdf45
Du-Harpur, Xinyi
7c173869-67ff-42ab-9d96-cc29baf7441d
Käpylä, Jarmo
f022928a-613a-4544-84f1-7bb10dc608a2
Nutt, Stephen L
037c1bc2-effa-4c15-a883-7a4571522b02
Salminen, Tiina A
e7a274db-e909-4356-b655-0738fdce490f
Heino, Jyrki
a6adad3d-5954-4abf-9483-c192ced4ecc0
Watt, Fiona M
24fff937-94b0-4127-8cbb-e8bd6e01fa29

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), 1453-1465.e7. (doi:10.1016/j.devcel.2022.05.011).

Record type: Article

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.

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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
ORCID for Kif Liakath-Ali: ORCID iD orcid.org/0000-0001-9047-7424

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Date deposited: 21 Jun 2024 17:09
Last modified: 22 Jun 2024 02:14

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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 ORCID iD
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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