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

Kalle Sipilä, Emanuel Rognoni, Johanna Jokinen, Mukul Tewary, Matteo Vietri Rudan, Salli Talvi, Ville Jokinen, Käthe M. Dahlström, Kif Liakath-Ali, Atefeh Mobasseri, Xinyi Du-Harpur, Jarmo Käpylä, Stephen L. Nutt, Tiina A. Salminen, Jyrki Heino, Fiona M. Watt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1453-1465.e7
JournalDevelopmental Cell
Volume57
Issue number12
DOIs
Publication statusPublished - 20 Jun 2022

Keywords

  • cell adhesion
  • ECM organization
  • fibronectin
  • integrin
  • lipid metabolism
  • SG differentiation
  • stem cell niche

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