2. Academic Validation
  3. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation

Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation

  • PLoS One. 2016 Dec 1;11(12):e0167392. doi: 10.1371/journal.pone.0167392.
Lianghua Bin 1 2,  Liehua Deng 1,  Hengwen Yang 1,  Leqing Zhu 1,  Xiao Wang 1,  Michael G Edwards 3,  Brittany Richers 2,  Donald Y M Leung 2 4
Affiliations

Affiliations

  • 1 The First Affiliated Hospital, Biomedical Translational Research Institute, the International Immunology Center and the Key Laboratory of Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong Province, China.
  • 2 Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
  • 3 Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, CO, United States of America.
  • 4 Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The State Key Clinical Specialty in Allergy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
PMID: 27907090 DOI: 10.1371/journal.pone.0167392
Abstract

The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC) terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq) profiling approach, we found that forkhead box c 1 (FOXC1) was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

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