In brief

A protein called CD10 in adipose-derived stem cells activates the formation of good fat cells, which can protect against metabolic diseases.

© A*STAR Research

Searching for good fat’s origins

14 Feb 2022

Researchers have identified a stem cell marker that influences fat cell development, unlocking exciting therapeutic opportunities for chronic diseases.

Due to its links to chronic disease, excess body fat has earned a bad reputation over the years. But not all fat cells, or adipocytes, are created equal. While the accumulation of ‘bad’ fat around internal organs isn't considered healthy, researchers believe that a distinct class of adipocytes located beneath the skin may help protect against chronic disease.

“Good adipocytes protect against developing metabolic diseases like diabetes and cardiovascular diseases by storing excess calories and secreting metabolically beneficial bioactive molecules,” said Shigeki Sugii, a Group Leader at A*STAR’s Institute of Bioengineering and Bioimaging (IBB).

Adipocytes develop from a population of progenitor cells called adipose-derived stem cells (ASCs). However, many of the biological processes that govern this maturation are unclear, and researchers still don't know which ASCs end up becoming 'good' adipocytes.

Hoping to bridge this gap and unlock new therapeutic targets, Sugii and his team took a closer look at ASC differentiation. Previously, Sugii’s group had identified that ASCs found under the skin's surface expressed a specific biomarker, a protein called CD10. Following up on these studies, the team hypothesized that the levels of CD10 expression could impact ASC's potential to mature into ‘good’ fat.

To test their theory, the team generated two genetically engineered ASC cell lines where the CD10 gene was either turned off or switched to overdrive. They then stimulated these cell lines to differentiate using a cocktail of growth factors. Using lipid droplet formation to measure adipocyte maturation, the scientists measured how CD10 impacted fat formation.

The role of CD10 as an orchestrator of fat development was evident. ASCs that lacked CD10 produced fewer lipid droplets than the control cells. On the other hand, those with abundant CD10 levels had significantly more mature adipocytes than control cells at the same time point.

Furthermore, the team uncovered a new aspect of adipocyte maturation. “It was generally believed that the adipocyte differentiation almost always involves a master regulator called PPARγ,” said Sugii. “But we showed that CD10 activates the formation of fat cells independent of PPARγ signaling pathways.”

Together, these findings suggest that CD10 may someday be used as a stem cell biomarker for predicting the quality of mature adipocytes from ASCs—with potential applications for treating metabolic conditions like obesity and diabetes.

According to Sugii, ASC populations that strongly express CD10 may be high-quality sources of 'good' adipocytes that could be transplanted in patients to reverse the adverse metabolic processes associated with the disease. Since their study, the team has patented their CD10 technology and is currently collaborating with industry partners to expand the clinical application boundaries of human ASC transplantation.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Bioengineering and Bioimaging (IBB).

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Chakraborty, S., Ong, W. K., Tau, W. W. Y., Zhou, Z., Bhanu Prakash, K. N., et al.  CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells, Stem Cell Research & Therapy 12, 109 (2021) | article

About the Researcher

Shigeki Sugii leads the Laboratory of Fat Metabolism and Stem Cells under the Cell Biology & Therapies Division at the Institute of Molecular and Cell Biology (IMCB). Sugii also holds a joint appointment at Duke-NUS Medical School. Before joining IMCB, he was a Group Leader at A*STAR's Singapore Bioimaging Consortium (SBIC) from 2011-2019 and at A*STAR's Institute of Bioengineering and Bioimaging (IBB) from 2019-2021. Sugii graduated with a B.S. in Agricultural Chemistry from Kyoto University, Japan and received his Ph.D. in Biochemistry at Dartmouth Medical School, USA. He then moved to the Salk Institute for Biological Studies and Howard Hughes Medical Institute, USA to conduct his postdoctoral research with Prof. Ronald Evans. Sugii serves as an executive committee member (Secretary) of the Stem Cell Society Singapore and on several other scientific committees. He was a co-founder of Celligenics Pte. Ltd. and recently founded ImpacFat Pte. Ltd. in Singapore.

This article was made for A*STAR Research by Wildtype Media Group