Method and composition used for obtaining neuron-like cells from non-neuronal cells via reprogramming

A technology of neuron-like cells and neurons, applied in the field of biomedicine, can solve problems such as low efficiency, complicated technical operations and practicality

Active Publication Date: 2015-11-11
PEKING UNIV +1
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  • Abstract
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Problems solved by technology

Nonetheless, low induction efficiency, technical complexity, and the risk of genomic integration with viral vector manipulations have raised concerns about the future utility of these methods

Method used

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  • Method and composition used for obtaining neuron-like cells from non-neuronal cells via reprogramming
  • Method and composition used for obtaining neuron-like cells from non-neuronal cells via reprogramming
  • Method and composition used for obtaining neuron-like cells from non-neuronal cells via reprogramming

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Embodiment Construction

[0139] The present invention will be further described in detail below in conjunction with specific embodiments, and the given examples are only for clarifying the present invention, not for limiting the scope of the present invention. The materials and reagents used in the following examples can be obtained from commercial sources unless otherwise specified. The experimental methods in the following examples are conventional methods unless otherwise specified. The following cells were all stored at 37°C in 5% (volume percent) CO 2 cultivated in an environment. I-BET151 used in all experiments in this application refers to I-BET151 hydrochloride, referred to as B.

[0140] definition

[0141] "Agonist" refers to a substance that can significantly enhance the expression or activity of a certain gene. An agonist can enhance gene expression or activity by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more compared to a control without agonist. In some cases, the expression ...

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Abstract

The invention discloses a method and a composition used for obtaining neuron-like cells from non-neuronal cells via reprogramming. The composition comprises a neuron-like characteristic chemical inducer; the neuron-like characteristic chemical inducer comprises an arbitrary combination of the following ingredients: 1) a cyclic adenosine monophosphate agonist; 2) neurogenic small molecules; 3) glycogen synthase kinase inhibitors, 4) TGF beta receptor inhibitors; 5) BET family bromodomain inhibitors; and 6) a selective inhibitor of Rho-associated, coiled-coil containing protein kinase and / or a p38 mitogen-activated protein kinase inhibitor; wherein 6) is a selective ingredient. The composition used for providing non-neuronal eukaryotic cells with neuron-like characteristics is capable of producing more than 90% TUJ1 positive cells in 16 days of induction. The neuron-like cells obtained via chemical induction possess neuronal specific expression profiles, are capable of generating action potential, and forming functional synapses via further maturation promotion.

Description

technical field [0001] The present invention relates to methods and compositions for reprogramming non-neuronal cells into neuron-like cells in the field of biomedicine. Background technique [0002] In regenerative medicine, a major problem is how to obtain customizable functional cell types. In recent years, direct lineage reprogramming has emerged as a promising new method for manipulating cell fate, which is fast and direct in manipulating cell fate, and can bypass the tumorigenic risks that may arise from manipulations involving pluripotent stem cells . Fibroblasts can be directly transformed into different types of functional cell types through virus-mediated known cell fate-determining transcription factors or microRNAs (Davisetal., 1987; Vierbuchenetal., 2010; Xuetal., 2015; Yooetal., 2011). This direct reprogramming method has been used in disease models, indicating potential important applications in regenerative medicine (Xue et al., 2015). Moreover, direct re...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/0793A61K35/30A61P25/00A61P25/14A61P25/28
CPCA61K9/0019A61K35/30A61P25/00A61P25/14A61P25/28C12N5/0619C12N2501/01C12N2501/115C12N2501/13C12N2501/15C12N2501/60C12N2501/727C12N2501/999C12N2502/086C12N2503/02C12N2506/08C12N2506/1307C12N5/0607C12N2506/1353C12N2506/1369C12N2506/1384C12N2506/1392
Inventor 邓宏魁李翔左潇含
Owner PEKING UNIV
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