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Recently, the Chinese Academy of Sciences Shanghai Institute of Life Sciences Institute of Biochemistry and Cell Biology Research Group of the latest research progress, with The Transcriptome analysis stages control human stem stem cell cell to neuron cells, published online in Journal of Biological Chemist.
The study divided the hESCs nerve differentiation process into five important stages based on the dynamic changes in the expression of the human embryonic stem cells (hESCs) genome, and found the key stages and core determining factors that determine the hESCs nerve differentiation process.
in the process of human embryo development, the appearance of the neuroblastatal layer occurs at the end of the third week of conception.
human embryonic stem cell neurodirective differentiation is an ideal in-body model for the study of early human neurodevelopment, but the molecular mechanism of hESCs nerve differentiation is not clear.
hESCs developed and differentiated into mature neurons without adding exogenous factors, which facilitated the phased study of the molecular mechanisms of stem cell fate decisions and neural processes in the human body. Using the established hESCs neurodifferentiation system, the
Jing Nai-Chi research team collected cell samples the first 22 days of neurodifferentiation and sequenced the collected cell samples.
data analysis showed that the differentiation process of hESCs to mature neurons followed the laws of neurodevelopment in the body, and the cell transcription group showed significant dynamic expression changes, with five distinct sexual expression gene modules (modules) appearing in turn.
based on the dynamic expression characteristics of these module genes, the researchers divided the hESCs nerve differentiation process into five stages, each of which identified marker genes corresponding to the specific nerve differentiation phase.
study also found that important cell signaling paths such as FGF, TGF-beta, WNT, HEDGEHOG, and NOTCH were in order to be active during the hESCs nerve differentiation process.
this data was further compared with published transcription group data and found that stage 3, which corresponds to differentiation to days 8-10, was a critical period for the neurodegeneration of pluripotent stem cells.
interestingly, there is no active signaling path at this stage, and through data analysis, the researchers have found transcription factors that play a key role in neurodegeneration decisions.
using CRISPR/Cas9 gene knockout techniques to study the function stakes of the key transcription factors SIX3 and HESX1 at this stage and found that they were necessary for the neural fate decisions of pluripotent stem cells.
, by studying the dynamic changes of phased transcription groups, the researchers expounded the molecular mechanism of hESCs neurodifferentiation from both intracellular gene expression and extracellular signaling pathways, which laid the foundation for inducing hESCs to be efficiently differentiated into specific neuronsubtypes and related conversion applications.
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