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CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells.

Publication ,  Journal Article
Chakraborty, S; Ong, WK; Yau, WWY; Zhou, Z; Bhanu Prakash, KN; Toh, S-A; Han, W; Yen, PM; Sugii, S
Published in: Stem Cell Res Ther
February 4, 2021

BACKGROUND: Effective stem cell therapy is dependent on the stem cell quality that is determined by their differentiation potential, impairment of which leads to poor engraftment and survival into the target cells. However, limitations in our understanding and the lack of reliable markers that can predict their maturation efficacies have hindered the development of stem cells as an effective therapeutic strategy. Our previous study identified CD10, a pro-adipogenic, depot-specific prospective cell surface marker of human adipose-derived stem cells (ASCs). Here, we aim to determine if CD10 can be used as a prospective marker to predict mature adipocyte quality and play a direct role in adipocyte maturation. METHODS: We first generated 14 primary human subject-derived ASCs and stable immortalized CD10 knockdown and overexpression lines for 4 subjects by the lentiviral transduction system. To evaluate the role of CD10 in adipogenesis, the adipogenic potential of the human subject samples were scored against their respective CD10 transcript levels. Assessment of UCP1 expression levels was performed to correlate CD10 levels to the browning potential of mature ASCs. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to determine CD10-dependent regulation of various targets. Seahorse analysis of oxidative metabolism and lipolysis assay were studied. Lastly, as a proof-of-concept study, we used CD10 as a prospective marker for screening nuclear receptor ligands library. RESULTS: We identified intrinsic CD10 levels as a positive determinant of adipocyte maturation as well as browning potential of ASCs. Interestingly, CD10 regulates ASC's adipogenic maturation non-canonically by modulating endogenous lipolysis without affecting the classical peroxisome proliferator-activated receptor gamma (PPARγ)-dependent adipogenic pathways. Furthermore, our CD10-mediated screening analysis identified dexamethasone and retinoic acid as stimulator and inhibitor of adipogenesis, respectively, indicating CD10 as a useful biomarker for pro-adipogenic drug screening. CONCLUSION: Overall, we establish CD10 as a functionally relevant ASC biomarker, which may be a prerequisite to identify high-quality cell populations for improving metabolic diseases.

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Published In

Stem Cell Res Ther

DOI

EISSN

1757-6512

Publication Date

February 4, 2021

Volume

12

Issue

1

Start / End Page

109

Location

England

Related Subject Headings

  • Stem Cells
  • Prospective Studies
  • PPAR gamma
  • Neprilysin
  • Humans
  • Cells, Cultured
  • Cell Differentiation
  • Adipogenesis
  • Adipocytes
  • 31 Biological sciences
 

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Chakraborty, S., Ong, W. K., Yau, W. W. Y., Zhou, Z., Bhanu Prakash, K. N., Toh, S.-A., … Sugii, S. (2021). CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells. Stem Cell Res Ther, 12(1), 109. https://doi.org/10.1186/s13287-021-02179-y
Chakraborty, Smarajit, Wee Kiat Ong, Winifred W. Y. Yau, Zhihong Zhou, K. N. Bhanu Prakash, Sue-Anne Toh, Weiping Han, Paul M. Yen, and Shigeki Sugii. “CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells.Stem Cell Res Ther 12, no. 1 (February 4, 2021): 109. https://doi.org/10.1186/s13287-021-02179-y.
Chakraborty S, Ong WK, Yau WWY, Zhou Z, Bhanu Prakash KN, Toh S-A, et al. CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells. Stem Cell Res Ther. 2021 Feb 4;12(1):109.
Chakraborty, Smarajit, et al. “CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells.Stem Cell Res Ther, vol. 12, no. 1, Feb. 2021, p. 109. Pubmed, doi:10.1186/s13287-021-02179-y.
Chakraborty S, Ong WK, Yau WWY, Zhou Z, Bhanu Prakash KN, Toh S-A, Han W, Yen PM, Sugii S. CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells. Stem Cell Res Ther. 2021 Feb 4;12(1):109.
Journal cover image

Published In

Stem Cell Res Ther

DOI

EISSN

1757-6512

Publication Date

February 4, 2021

Volume

12

Issue

1

Start / End Page

109

Location

England

Related Subject Headings

  • Stem Cells
  • Prospective Studies
  • PPAR gamma
  • Neprilysin
  • Humans
  • Cells, Cultured
  • Cell Differentiation
  • Adipogenesis
  • Adipocytes
  • 31 Biological sciences