Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest

PLoS One. 2013 Dec 31;8(12):e84206. doi: 10.1371/journal.pone.0084206. eCollection 2013.

Abstract

Recent studies have shown that adipose-derived stromal/stem cells (ASCs) contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs). This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2) and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta). NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Analysis of Variance
  • Animals
  • Biomarkers / metabolism
  • Cell Lineage / physiology*
  • Immunohistochemistry
  • Integrases
  • Mice
  • Mice, Transgenic
  • Neural Crest / cytology*
  • Real-Time Polymerase Chain Reaction
  • Stem Cells / cytology*
  • Stromal Cells / cytology*

Substances

  • Biomarkers
  • Cre recombinase
  • Integrases

Grant support

This research was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#24791913; http://www.jsps.go.jp/j-grantsinaid/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.