‘Self-eating’ stem cell process may be the key to new regenerative therapies
A Penn study uncovers new roles of chaperone-mediated autophagy in how stem cells repair or regenerate damaged organs.
The self-eating process in embryonic stem cells known as chaperone-mediated autophagy (CMA) and a related metabolite may serve as promising new therapeutic targets to repair or regenerate damaged cells and organs, Penn Medicine researchers show in a new study published online in Science.
A translucently colored embryonic stem (ES) cell and its differentiating derivatives. (Image: Penn Medicine News)
Human bodies contain more than 200 different types of specialized cells. All of them can be derived from embryonic stem (ES) cells, which relentlessly self-renew while retaining the ability to differentiate into any cell type in adult animals, a state known as pluripotency. Researchers have known that the cells’ metabolism plays a role in this process; however, it wasn’t clear exactly how the cells’ internal wiring works to keep that state and ultimately decide stem cell fate.
The new preclinical study, for the first time, shows how the stem cells keeps CMA at low levels to promote that self-renewal, and when the stem cell is ready, it switches that suppression off to enhance CMA, among other activities, and differentiate into specialized cells.
“It’s an intriguing discovery in the field of stem cell biology and for researchers looking to develop therapies for tissue or organ regeneration,” says senior author Xiaolu Yang, a professor of cancer biology at the Abramson Family Cancer Research Institute in the Perelman School of Medicine. “We reveal two novel ways to potentially manipulate the self-renewal and differentiation of stem cells: CMA and a metabolite, known as alpha-ketoglutarate, that is regulated by CMA. Rationally intervening or guiding these functions could be a powerful way to increase the efficiency of regenerative medicine approaches.”
Griffin Pitt, right, works with two other student researchers to test the conductivity, total dissolved solids, salinity, and temperature of water below a sand dam in Kenya.
Griffin Pitt’s upbringing made her passionate about water access and pollution, and Penn has given her the opportunity to explore these issues back home in North Carolina and abroad.
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