Direct reprogramming of epidermal cells toward sweat gland-like cells by defined factors

Cell Death Dis. 2019 Mar 20;10(4):272. doi: 10.1038/s41419-019-1503-7.

Abstract

Several studies have reported inducing adult cells into sweat gland-like cells; however, slow transition and low efficiency limit the potential for cell-based treatment. Here, we show that overexpression of the transcription factor FoxC1 was sufficient to reprogram epidermal cells to induced functional sweat gland-like cells (iSGCs). The iSGCs expressing secreting-related genes, had a global gene expression profile between fetal SGCs (P5) and adult SGCs (P28). Moreover, iSGCs transplanted into the burn mice model facilitated wound repair and sweat gland regeneration. We further demonstrated that the Foxc1 upregulated BMP5 transcription and BMP5 is responsible for the cell-type transition. Collectively, this study shows that lineage reprogramming of epidermal cells into iSGCs provides an excellent cell source and a promising regenerative strategy for anhidrosis and hypohidrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 5 / genetics
  • Bone Morphogenetic Protein 5 / metabolism
  • Burns / metabolism
  • Burns / therapy
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cell Transplantation / methods
  • Cellular Reprogramming / genetics*
  • Epidermal Cells / metabolism*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Knockdown Techniques
  • Hypohidrosis / therapy
  • Interferon Regulatory Factors / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Repressor Proteins / metabolism
  • Sweat Glands / cytology*
  • Transcriptome
  • Transfection
  • Wound Healing / physiology

Substances

  • Bmp5 protein, mouse
  • Bone Morphogenetic Protein 5
  • Forkhead Transcription Factors
  • Foxc1 protein, mouse
  • IRF6 protein, mouse
  • Interferon Regulatory Factors
  • Repressor Proteins
  • Tfcp2l1 protein, mouse