A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α

Stem Cells. 2019 Nov;37(11):1441-1454. doi: 10.1002/stem.3067. Epub 2019 Aug 14.

Abstract

In a previous study, we showed that folate receptor-α (FRα) translocates to the nucleus where it acts as a transcription factor and upregulates Hes1, Oct4, Sox2, and Klf4 genes responsible for pluripotency. Here, we show that acetylation and phosphorylation of FRα favor its nuclear translocation in the presence of folate and can cause a phenotypic switch from differentiated glial cells to dedifferentiated cells. shRNA-FRα mediated knockdown of FRα was used to confirm the role of FRα in dedifferentiation. Ocimum sanctum hydrophilic fraction-1 treatment not only blocks the folate mediated dedifferentiation of glial cells but also promotes redifferentiation of dedifferentiated glial cells, possibly by reducing the nuclear translocation of ~38 kDa FRα and subsequent interaction with chromatin assembly factor-1. Stem Cells 2019;37:1441-1454.

Keywords: Cranial neural crest cells; Dedifferentiation; Differentiation; Folate receptor alpha; Oct4; Sox2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Dedifferentiation / drug effects
  • Cell Dedifferentiation / genetics
  • Cell Line
  • Cell Line, Tumor
  • Folate Receptor 1 / genetics
  • Folate Receptor 1 / metabolism*
  • Folic Acid / analogs & derivatives
  • Folic Acid / pharmacology
  • Humans
  • Kruppel-Like Factor 4
  • Neural Crest / drug effects*
  • Neural Crest / metabolism*
  • Neuroglia / drug effects*
  • Neuroglia / metabolism*
  • Nuclear Transfer Techniques
  • Ocimum sanctum / chemistry
  • Octamer Transcription Factor-3 / metabolism
  • RNA, Small Interfering / genetics
  • SOXB1 Transcription Factors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • CNOT8 protein, human
  • Folate Receptor 1
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • SOXB1 Transcription Factors
  • Transcription Factors
  • 5,11-methenyltetrahydrohomofolate
  • Folic Acid