Finds mechanism of control of cells responsible for the regeneration of human tissues

(ORDO NEWS) — An international team of scientists has discovered a mechanism that allows stem cells to decide on the fate of daughter cells even during division.

The data obtained will help in the development of new ways to stimulate tissue regeneration to accelerate recovery from damage, and possibly for the treatment of degenerative diseases.

Tissue stem cells are found in a large number of tissues in our body. They are responsible for the regeneration of these tissues and can become any cell that is characteristic of the particular tissue in which it is located.

This property is called multipotency, in contrast to the pluripotency of embryonic stem cells, which can become any cell of the whole organism – even a neuron, even a myocyte (muscle tissue cell).

finds mechanism of control of cells responsible for the regeneration of human tissuesFluorescent microscope images show immunofluorescence (IF) staining of the RISP protein in mitochondrial domains enriched in old or new labels. / © Döhla J., et al., Nature Cell Biology, 2022

When a stem cell divides, two daughter cells are formed, which can be either stem or differentiated tissue cells.

The new work of researchers from the University of Helsinki (Finland), as well as their colleagues from Sweden and Germany, is devoted to studying the mechanism according to which daughter stem cells determine whether to differentiate or remain stem cells.

More precisely, the fate of daughter cells is affected by uneven inheritance of mitochondria from the parent cell.

When studying the division of epithelial stem cells, scientists found that if a daughter cell gets a lot of old, but more active mitochondria, it loses the ability to self-renew and differentiates into a cell that supports the function of the epithelium. At the same time, another daughter cell, which received younger mitochondria, continues to live as a stem cell.

The thing is that in newly synthesized mitochondria there is a low level of a special iron-sulfur protein involved in the electron transport chain, an important step in cellular respiration.

Because of this, in organelles, glucose is oxidized to a greater extent along the alternative (relative to standard glycolysis) pentose phosphate pathway, which allows the daughter cell to remain a stem cell. In the second cell, more mature mitochondria take full advantage of normal glycolysis to oxidize glucose and provide energy, which promotes cell differentiation.

finds mechanism of control of cells responsible for the regeneration of human tissuesSchematic description of the experiment. New and old mitochondria were distinguished using fluorescent labels / © Döhla J., et al., Nature Cell Biology, 2022

“The inclusion of genes that determine cellular functions ultimately determines cell differentiation, but metabolism, apparently, is the very first factor influencing their fate,” says Associate Professor Pekka Katajisto from the Helsinki Institute of Life Sciences (HiLIFE ) University of Helsinki.

“When we limited cellular respiration by reducing the amount of one protein abundant in old mitochondria, the daughter cells were effectively self-renewing stem cells,” adds researcher Julia Govenius of the University of Helsinki.

Their work clearly demonstrates that even small differences in the protein composition of mitochondria can affect the metabolism of whole cells and, as a result, the fate of these cells in tissues.

This discovery is part of fundamental research that lays the foundation for the development of new ways to stimulate tissue regeneration (for example, in degenerative diseases) or to accelerate recovery after tissue damage.

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