Characterization of adipocyte differentiation from human mesenchymal stem cells in bone marrow

Shu Wen Qian, Xi Li, You You Zhang, Hai Yan Huang, Yuan Liu, Xia Sun, Qi Qun Tang

Research output: Contribution to journalArticle

Abstract

Background. Adipocyte hyperplasia is associated with obesity and arises due to adipogenic differentiation of resident multipotent stem cells in the vascular stroma of adipose tissue and remote stem cells of other organs. The mechanistic characterization of adipocyte differentiation has been researched in murine pre-adipocyte models (i.e. 3T3-L1 and 3T3-F442A), revealing that growth-arrest pre-adipocytes undergo mitotic clonal expansion and that regulation of the differentiation process relies on the sequential expression of three key transcription factors (C/EBP, C/EBP and PPAR). However, the mechanisms underlying adipocyte differentiation from multipotent stem cells, particularly human mesenchymal stem cells (hBMSCs), remain poorly understood. This study investigated cell cycle regulation and the roles of C/EBP, C/EBP and PPAR during adipocyte differentiation from hBMSCs. Results. Utilising a BrdU incorporation assay and manual cell counting it was demonstrated that induction of adipocyte differentiation in culture resulted in 3T3-L1 pre-adipocytes but not hBMSCs undergoing mitotic clonal expansion. Knock-down and over-expression assays revealed that C/EBP, C/EBP and PPAR were required for adipocyte differentiation from hBMSCs. C/EBP and C/EBP individually induced adipocyte differentiation in the presence of inducers; PPAR alone initiated adipocyte differentiation but the cells failed to differentiate fully. Therefore, the roles of these transcription factors during human adipocyte differentiation are different from their respective roles in mouse. Conclusions. The characteristics of hBMSCs during adipogenic differentiation are different from those of murine cells. These findings could be important in elucidating the mechanisms underlying human obesity further.

Original languageEnglish (US)
Article number47
JournalBMC Developmental Biology
Volume10
DOIs
StatePublished - 2010
Externally publishedYes

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Mesenchymal Stromal Cells
Adipocytes
Bone Marrow
Peroxisome Proliferator-Activated Receptors
Multipotent Stem Cells
Transcription Factors
Obesity
Bromodeoxyuridine
Hyperplasia
Blood Vessels
Adipose Tissue
Cell Differentiation
Cell Cycle
Stem Cells

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Characterization of adipocyte differentiation from human mesenchymal stem cells in bone marrow. / Qian, Shu Wen; Li, Xi; Zhang, You You; Huang, Hai Yan; Liu, Yuan; Sun, Xia; Tang, Qi Qun.

In: BMC Developmental Biology, Vol. 10, 47, 2010.

Research output: Contribution to journalArticle

Qian, Shu Wen ; Li, Xi ; Zhang, You You ; Huang, Hai Yan ; Liu, Yuan ; Sun, Xia ; Tang, Qi Qun. / Characterization of adipocyte differentiation from human mesenchymal stem cells in bone marrow. In: BMC Developmental Biology. 2010 ; Vol. 10.
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abstract = "Background. Adipocyte hyperplasia is associated with obesity and arises due to adipogenic differentiation of resident multipotent stem cells in the vascular stroma of adipose tissue and remote stem cells of other organs. The mechanistic characterization of adipocyte differentiation has been researched in murine pre-adipocyte models (i.e. 3T3-L1 and 3T3-F442A), revealing that growth-arrest pre-adipocytes undergo mitotic clonal expansion and that regulation of the differentiation process relies on the sequential expression of three key transcription factors (C/EBP, C/EBP and PPAR). However, the mechanisms underlying adipocyte differentiation from multipotent stem cells, particularly human mesenchymal stem cells (hBMSCs), remain poorly understood. This study investigated cell cycle regulation and the roles of C/EBP, C/EBP and PPAR during adipocyte differentiation from hBMSCs. Results. Utilising a BrdU incorporation assay and manual cell counting it was demonstrated that induction of adipocyte differentiation in culture resulted in 3T3-L1 pre-adipocytes but not hBMSCs undergoing mitotic clonal expansion. Knock-down and over-expression assays revealed that C/EBP, C/EBP and PPAR were required for adipocyte differentiation from hBMSCs. C/EBP and C/EBP individually induced adipocyte differentiation in the presence of inducers; PPAR alone initiated adipocyte differentiation but the cells failed to differentiate fully. Therefore, the roles of these transcription factors during human adipocyte differentiation are different from their respective roles in mouse. Conclusions. The characteristics of hBMSCs during adipogenic differentiation are different from those of murine cells. These findings could be important in elucidating the mechanisms underlying human obesity further.",
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AU - Sun, Xia

AU - Tang, Qi Qun

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