动物造模 z-bio 2022-02-14 268

　　Once it grows, it will last a lifetime. Even if some parts are worn out, there is almost no possibility of replacement. This is the human nervous system. This characteristic has brought endless troubles to human beings: some functional impairments lead to blindness and paralysis, and some degenerative changes cause Parkinson's disease and Alzheimer's disease... Recently, scientists in Shanghai have used the latest gene editing technology to unearth the The potential of nerve cells to transform into "super-substitutes" has brought a new dawn to the treatment of nerve damage and neurodegenerative diseases. Late last night, the international authoritative academic journal "Cell" published the results of the Shanghai scientists online.

　　This time, it is a class of nerve cells called glial cells that have been given "super-substitute" potential by scientists. There are a large number of these cells, and their main job is to provide nutrients to neurons, which is quite "leisure". "Why not extract some glial cells from the patient's body and transform them into neurons that can undertake more important tasks?" Five years ago, Yang Hui, a researcher at the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences, came up with this idea.

　　In real life, it is too difficult to find a "replacement" for damaged or prematurely degenerated neurons: the use of embryonic stem cells has ethical issues, the use of induced pluripotent stem cells is too easy to induce tumors, and the direct transplantation of nerve cells is prone to rejection and There will also be problems with survival and integration... "If the idea of finding a 'substitute' can be realized, it will benefit tens of millions of patients." Yang Hui said, for example, many eye diseases, such as glaucoma and ischemic retinopathy, will cause optic ganglion cells death, which can lead to permanent blindness. According to statistics, the number of blind people caused by glaucoma alone exceeds 10 million in the world.

　　This is also a highly competitive field in the world. Yang Hui's research group, who is good at gene editing technology, has explored a unique path: they have discovered a small RNA editing tool from foreign scientific research reports, which can safely enter the organism for gene editing. Editing, so that glial cells into pluripotent stem cells, and then re-differentiate into the neuronal cells scientists need.

　　Zhou Haibo, the co-corresponding author of the paper and a postdoctoral fellow at the Center of Excellence for Brain Intelligence, Chinese Academy of Sciences, introduced that they first designed specifically labeled Muller glial cells and their expression CasRx system (a gene editing system) in in vitro cells, and then "packaged all the components" "Injected under the retina of mice with permanent vision impairment due to damage to optic ganglion cells. About a month later, they were pleasantly surprised to find that the blind mice regained light perception—meaning that optic ganglion cells transdifferentiated from Müller glial cells can respond to light stimulation just like normal cells, and It also establishes a functional connection to the correct brain area through the optic nerve, which transmits visual signals to the brain.

　　The technique was also successful in a mouse model of Parkinson's disease. Parkinson's disease is primarily caused by the loss of dopamine neuron death in the substantia nigra of the brain. This time, the researchers took a fancy to the astrocytes in the striatum in the lower brain region of the substantia nigra, and transdifferentiated some of them into dopamine neuron cells, successfully making up for the function of the lost dopamine neurons in the substantia nigra— - The exercise capacity of mice with Parkinson's disease was significantly improved.

　　Cell reviewers believe that the study "presents an elegant and exciting case" and "shows a fresh perspective with potential wide-ranging applications." Pu Muming, academician of the Chinese Academy of Sciences and academic director of the Center for Brain Intelligence Excellence of the Chinese Academy of Sciences, said that the research will be advanced into non-human primate experiments as soon as possible.