The unexpected role of fat in the fate of muscle stem cells

Satellite cells differentiate into muscle cells or self-renew depending on the level of lipid droplets in the cell. Shihuan Kwang, a professor of animal sciences at Purdue University, has shown for the first time that lipids within adult muscle stem cells regulate their fate. Credit: Purdue University/Shihuan Kwang

Scientists have shown for the first time that the fats inside adult muscle stem cells regulate their fate.

“No one has seen such dynamics of fat droplets in these muscle stem cells, so this finding is very exciting,” said Purdue University professor of animal sciences, Shihuan Quang, who led the team of scientists. “The finding that they play such a powerful role in stem cell fate is remarkable. It has potential implications for muscle disease, aging and animal science.”

Cells contain different types of lipids, or lipids, that are essential for energy production, cell membrane formation, and chemical signaling. Special structures, called lipid droplets, store these cellular lipids safely.

Rather than existing as a fixed set of resources, the researchers discovered that the number of these droplets varies greatly in an individual cell and varies from cell to cell. The number of drops also regulates the shape of the stem cells.

This finding, combined with newly identified roles for lipids in other types of stem cells — including cancer stem cells — suggests that lipids may be involved in much more than previously thought, Kwang said. The results are detailed in a paper in the journal cell reports.

Purdue’s team studied satellite cells, a group of stem cells responsible for muscle growth, growth, and regeneration. In adult muscle, these cells are kept dormant until an injury occurs and they are called into action. They then multiply through divisions and some of the dividing cells become muscle cells to replace the damaged cells, in a process called differentiation. Others return to hibernation through a process called self-renewal.

“Our study showed that stem cells with larger numbers of lipid droplets continued to divide or continued to differentiate into muscle cells, and those with lower numbers returned to replenish the stocks of underlying stem cells following injury,” Kwang said. “In fact, during self-renewal, they somehow deplete or get rid of droplets of fat, and in an idle state they don’t have any.”

They discovered that upon activation, droplets appear, and as each cell divides, the lipid droplets are not always evenly distributed. Some cells descended from mitosis contain more droplets than others, and this asymmetric distribution leads to segregation of cell fate into self-renewal or differentiation.

“The dynamics of these lipid droplets are essential to maintaining a healthy cell balance,” Kwang said. “We need new muscle cells for repair, but we don’t want stem cells to divide uncontrollably, as happens in cancer. Exhausting lipid droplets is like a brake to stop uncontrolled proliferation.”

In previous studies, Kwang’s research team focused on muscle and fat cells.

“Because we also study fat cells called adipocytes, we have the tools to make this discovery,” he said. “During some routine staining of the cells, Feng Yue, a postdoctoral researcher on our team, observed the dynamics of lipid droplets in stem cells. This was surprising because they were not known to be abundant and dynamic in these cells, at the time. We thought ‘Why are they here? ?” We should have known.

The team used skeletal muscle stem cells in culture and a mouse model to determine the function of fat droplets. The team blocked lipid droplets from forming and then using them to see how these changes would affect cell function.

“The results were amazing because too many or too few lipid droplets disrupted the stem cell balance,” said Yu, who is now an assistant professor at the University of Florida. “This suggests that in the future we may be able to stimulate the regenerative function of stem cells by manipulating the dynamics of lipid droplets in satellite cells.”

Team members and co-authors also include Stephanie N. Obresco, a graduate student in the Department of Biological Sciences. Jiamin Qiu, Lijie Gu, Lijia Zhang, and Jingjuan Chen, animal science graduate students; Nagarajan Narayanan, Postdoctoral Researcher in Agricultural and Biological Engineering; and Meng Deng, associate professor of agricultural and biological engineering.

Kwang plans to further study the role of fat droplets in muscle repair.

“We do not yet fully understand the key regulators and mediators of fat droplets in muscle stem cells,” he said. “There may be secondary metabolites formed from the breakdown of lipid droplets which are also important. These lipids may be much more than an energy source for the cell.”

Lipid droplets as intracellular microlenses

more information:
Feng Yue et al, Dynamics of lipid droplets regulating the fate of adult muscle stem cells, cell reports (2022). DOI: 10.1016 / j.celrep.2021.110267

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