Composition and method for reprogramming human astrocytes into neurons or brain-like organs

Abstract

The invention belongs to the technical field of biology, and relates to a composition and method for reprogramming human astrocytes into neurons or brain-like organs. The composition for efficiently reprogramming human astrocytes into neurons comprises a substance capable of realizing OCT4 overexpression, a substance knocking down a cell cycle regulation factor p53, and a small molecule drug capable of inducing human astrocytes to be reprogrammed into neurons, wherein the small molecule drug capable of inducing the human astrocytes to be reprogrammed into the neurons is selected from one or more of the following four small molecule drugs: CHIR99021, SB431542, RepSox or Y27632. Compared with the prior art, the composition and method have the following advantages: regulation and control of two genes are combined; a brand-new small molecular medicine composition capable of efficiently reprogramming human astrocytes into neurons and brain-like organs is obtained through a large amount of screening; and reliability of the system obtained through screening is verified on astrocytes differentiated from human embryonic stem cells H9 and astrocytes of para-tumor tissues of glioma patients.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a composition and method for reprogramming human astrocytes into neurons or brain organoids. Background technique [0002] In 2017, Stem Cell Reports published online the research paper "Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules" by Pei Gang's research group at the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, reporting the use of a combination of small molecule compounds to achieve the A study of the direct transformation of astrocytes into nerve cells. [0003] Academician Pei Gang's research group used six small molecule drugs to reprogram human astrocytes into functional neurons, figure 1 A diagram of the technical scheme. The specific scheme is: inoculate human adult astrocytes in astrocyte growth medium (AM) pretreated with poly-lysine. Two days later, the cells reached 90% density, and the growt...

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Problems solved by technology

[0005] Although the technology of Pei Gang's research group as mentioned above is the technology disclosed in Chinese patent CN111073855A, which can reprogram human astrocytes into neurons, there are still some defects in the application of this reprogramming method to central nervous tissue regeneration, such as : (1) Astrocytes are directly reprogrammed into post-mitotic neurons that cannot proliferate in large quantities, so a large number of target neurons cannot be obtained; (2) Such reprogrammed cells do not have the ability to self-assemble to form human brain tissue capabilities, such as brain organoids, etc.; (3) This reprogramming method is a 2D system that does not have 3D brain tissue structure and functional connections

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