胚胎干细胞 z-bo 2020-10-07 265

　　In a new study, researchers at the Perelman School of Medicine at the University of Pennsylvania discovered that an autophagy process called CMA (molecular chaperone autophagy) in embryonic stem cells can be used for repair or regeneration.

　　The human body contains more than 200 special cells. All these cells can differentiate from embryonic stem cells (ESC). Embryonic stem cells continue to renew themselves while maintaining the ability to differentiate into all adult cell types. This condition is called pluripotency. Scientists already know that cell metabolism plays a specific role in this process, but how the internal circuits of cells maintain this state and ultimately determine the fate of stem cells. Whether this is done is still unknown.

　　This new preclinical study shows for the first time how embryonic stem cells maintain low levels of CMA and promote this self-renewal, manipulating the self-renewal and differentiation of embryonic stem cells to shut them down 2 has revealed two new methods to enhance CMA activity And prevent them from differentiating into specialized cells.

　　The corresponding author of this article, Dr. Yang Xiaolu, Professor of Cancer Biology at the Perelman School of Medicine at the University of Pennsylvania, said: "For those who want to develop tissue or organ regeneration therapy, this is an interesting discovery in the field of stem cell biology. Two new methods that may manipulate the self-renewal and differentiation of embryonic stem cells: regulated by CMA and CMA. Reasonable intervention or guidance of a metabolite called α-ketoglutarate on these functions may improve regeneration and a medical approach A powerful method of efficiency."

　　Autophagy is the most common. This is a feeding mechanism necessary for the survival and operation of organisms. When the cell autophagy, the substance inside the cell is delivered to the liposome. Lysosomes are organelles that help break down these substances. There are several forms of autophagy. However, unlike all other forms present in eukaryotic cells, CMA is unique to mammals. So far, the physiological role of CMA is still unknown. These researchers use mouse embryonic stem cell metabolism and genetic experimental techniques to better understand pluripotency and the major changes that occur during subsequent differentiation. These researchers found that the two basic pluripotent cytokines Oct4 and Sox2 blocked the gene called LAMP2A required for CAMP production, thereby minimizing CMA activity. A protein called lysosomal-associated membrane protein 2 provides instructions. They found that this lowest CMA activity allows embryonic stem cells to maintain high levels of α-ketoglutarate. It is an important metabolite that increases cell pluripotency. For differentiation, the reduction of Oct4 and Sox2 will cause embryonic stem cells to start to up-regulate CMA. The enhanced CMA activity leads to the degradation of key enzymes involved in the production of alpha-ketoglutarate. This reduces the level of α-ketoglutarate and increases the activity of other cells that promote differentiation. These findings indicate that CMA and α-ketoglutarate determine the fate of embryonic stem cells. Embryonic stem cells are often called pluripotent stem cells because they can produce all cell types in the human body except the placenta and umbilical cord. Embryonic stem cells not only provide an excellent system for studying the early development of mammals, but also have great potential in the development of regenerative therapies for the treatment of various human diseases. In the past decade, stem cell-based regenerative medicine therapies have developed rapidly. Studies have shown that damaged heart tissue can be repaired, solid organ transplantation can replace cells, and in some cases can treat neurological diseases.

　　Yang said: "The newly discovered role of autophagy in embryonic stem cells is the beginning of further research and can guide researchers, doctors and scientists to better treat various diseases."