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    Home > Active Ingredient News > Study of Nervous System > Deng Hongkui's team and others realized the chemical reprogramming of astrocytes into neurons in vivo

    Deng Hongkui's team and others realized the chemical reprogramming of astrocytes into neurons in vivo

    • Last Update: 2021-03-23
    • Source: Internet
    • Author: User
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    Written | Edited by Wang Cong | Nagisha Typesetting | Hydrological cell fate regulation is a basic process in biology.
    Artificial induced pluripotent stem cell technology represented by iPS can generate cell types required for regenerative medicine.

    The use of chemical methods for reprogramming is a new advancement in the field of cell fate regulation, reprogramming somatic cells into pluripotent stem cells through small molecule compounds.

    In addition, different functional lineages can also be generated through in vitro chemically induced cell lineage reprogramming.

    The chemical small molecule method has unique advantages such as high cell passability, reversibility and ease of operation in cell fate regulation, so this method has become a promising new strategy for cell fate regulation.

    Reprogramming of cell fate in vivo can compensate for cell loss by transforming cells in situ, which solves the various difficulties faced by transplanted cells.
    Moreover, the favorable environment in natural tissues can also promote the functional maturity and timely integration of reprogrammed cells in vivo.

    In mammals, many organs lack strong regenerative capacity.

     Cells lost in damaged tissues may be compensated by reprogramming in the body to transform nearby cells in situ.

    Cell reprogramming induced by chemical small molecules provides a time-flexible and non-integrated strategy for changing cell fate, which is advantageous for in vivo reprogramming in organs with extremely poor regenerative capacity (such as the brain).

    On March 2, 2021, Deng Hongkui's team from Peking University published a research paper titled: In vivo chemical reprogramming of astrocytes into neurons in Cell Discovery magazine.

    The study proved that in the brains of adult mice, small molecules can reprogram astrocytes into neurons.

    In terms of neuron-specific marker expression, electrophysiological properties and synaptic connectivity, in situ chemically induced neurons are similar to endogenous neurons.

    This study demonstrates the feasibility of in vivo chemical reprogramming in adult mouse brains and provides a new potential method for repairing the brain through neuronal regeneration.

    Due to its limited regenerative capacity, the mammalian central nervous system is an ideal target for evaluating chemical reprogramming in vivo, and glial cells (such as astrocytes) can potentially be used to generate neurons by in situ in vivo reprogramming.

    At present, the loss of neurons due to brain trauma or neurodegeneration is irreversible.
    Astrocytes are the most widely distributed type of cells in the mammalian brain.
    They can respond, proliferate and assemble to envelop necrotizing lesions, making them Ideal target for reprogramming in vivo.

    Therefore, a chemical method was developed to convert astrocytes into functional neurons in situ, which may help to integrate newly generated cells into natural neuronal tissue in time.

    Deng Hongkui’s team and others have confirmed in previous studies that simply using a combination of small molecules: Forskolin, ISX9, CHIR99021 and I-BET151 (FICB), can effectively transform mouse fibroblasts into functional neurons in vitro by chemical programming .

    In this study, the research team further developed a new combination of small molecules on the basis of the previous ones: DBcAMP, Forskolin, ISX9, CHIR99021, I-BET151 and Y-27632 (DFICBY) can achieve in vivo chemistry more efficiently Reprogramming can reprogram the astrocytes in the adult mouse brain into neurons with synaptic connectivity, called chemically induced neurons (CiNs).

    In addition, the research team further discovered that the medium supplemented with bFGF is important for cell survival and neuronal transformation.

    In order to enhance the application potential of chemically induced in vivo reprogramming, further improvements in drug delivery strategies are needed.

    Controlled drug release technology, including micron carriers, can achieve sustained release of drugs through one injection, thereby avoiding damage to the brain.

    In addition, effective delivery strategies can also improve efficiency.

    Link to the paper: https:// Open for reprint 
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