Glial-like differentiation potential of human mature adipocytes

J Mol Neurosci. 2015 Jan;55(1):91-98. doi: 10.1007/s12031-014-0345-0. Epub 2014 Jul 10.

Abstract

The potential ability to differentiate dedifferentiated adipocytes into a neural lineage is attracting strong interest as an emerging method of producing model cells for the treatment of a variety of neurological diseases. Here, we describe the efficient conversion of dedifferentiated adipocytes into a neural-like cell population. These cells grew in neurosphere-like structures and expressed a high level of the early neuroectodermal marker Nestin. These neurospheres could proliferate and express stemness genes, suggesting that these cells could be committed to the neural lineage. After neural induction, NeuroD1, Sox1, Double Cortin, and Eno2 were not expressed. Patch clamp data did not reveal different electrophysiological properties, indicating the inability of these cells to differentiate into mature neurons. In contrast, the differentiated cells expressed a high level of CLDN11, as demonstrated using molecular method, and stained positively for the glial cell markers CLDN11 and GFAP, as demonstrated using immunocytochemistry. These data were confirmed by quantitative results for glial cell line-derived neurotrophic factor production, which showed a higher secretion level in neurospheres and the differentiated cells compared with the untreated cells. In conclusion, our data demonstrate morphological, molecular, and immunocytochemical evidence of initial neural differentiation of mature adipocytes, committing to a glial lineage.

MeSH terms

  • Action Potentials
  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipocytes / physiology
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Claudins / genetics
  • Claudins / metabolism
  • Doublecortin Domain Proteins
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Nestin / genetics
  • Nestin / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology
  • Neurogenesis*
  • Neuroglia / cytology*
  • Neuroglia / metabolism
  • Neuroglia / physiology
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CLDN11 protein, human
  • Claudins
  • Doublecortin Domain Proteins
  • Glial Fibrillary Acidic Protein
  • Microtubule-Associated Proteins
  • NEUROD1 protein, human
  • Nestin
  • Neuropeptides
  • SOX1 protein, human
  • SOXB1 Transcription Factors
  • Phosphopyruvate Hydratase