Cell density-dependent transcriptional activation of endocrine-related genes in human adipose tissue-derived stem cells

Sagar Ghosh, Angela Dean, Marc Walter, Yongde Bao, Yanfen Hu, Jianhua Ruan, Rong Li

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Adipose tissue is recognized as an endocrine organ that plays an important role in human diseases such as type II diabetes and cancer. Human adipose tissue-derived stem cells (ASCs), a distinct cell population in adipose tissue, are capable of differentiating into multiple lineages including adipogenesis. When cultured in vitro under a confluent condition, ASCs reach a commitment stage for adipogenesis, which can be further induced into terminally differentiated adipocytes by a cocktail of adipogenic factors. Here we report that the confluent state of ASCs triggers transcriptional activation cascades for genes that are responsible for the endocrine function of adipose tissue. These include insulin-like growth factor 1 (IGF-1) and aromatase (Cyp19), a key enzyme in estrogen biosynthesis. Despite similar adipogenic potentials, ASCs from different individuals display huge variations in activation of these endocrine-related genes. Bioinformatics and experimental data suggest that transcription factor Foxo1 controls a large number of "early" confluency-response genes, which subsequently induce "late" response genes. Furthermore, siRNA-mediated knockdown of Foxo1 substantially compromises the ability of committed ASCs to stimulate tumor cell migration in vitro. Thus, our work suggests that cell density is an important determinant of the endocrine potential of ASCs.

Original languageEnglish (US)
Pages (from-to)2087-2098
Number of pages12
JournalExperimental Cell Research
Volume316
Issue number13
DOIs
StatePublished - Aug 2010

Fingerprint

Transcriptional Activation
Adipose Tissue
Stem Cells
Cell Count
Genes
Adipogenesis
Aromatase
Somatomedins
Computational Biology
Adipocytes
Type 2 Diabetes Mellitus
Small Interfering RNA
Cell Movement
Neoplasms
Estrogens
Transcription Factors
Enzymes
Population

Keywords

  • Adipogenesis commitment
  • Adipose stem cells
  • Aromatase
  • Cell confluency
  • Foxo1
  • Gene expression profiling
  • SBSN

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cell density-dependent transcriptional activation of endocrine-related genes in human adipose tissue-derived stem cells. / Ghosh, Sagar; Dean, Angela; Walter, Marc; Bao, Yongde; Hu, Yanfen; Ruan, Jianhua; Li, Rong.

In: Experimental Cell Research, Vol. 316, No. 13, 08.2010, p. 2087-2098.

Research output: Contribution to journalArticle

Ghosh, Sagar ; Dean, Angela ; Walter, Marc ; Bao, Yongde ; Hu, Yanfen ; Ruan, Jianhua ; Li, Rong. / Cell density-dependent transcriptional activation of endocrine-related genes in human adipose tissue-derived stem cells. In: Experimental Cell Research. 2010 ; Vol. 316, No. 13. pp. 2087-2098.
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