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Transcriptional Regulation Analysis In Somatic Induced Pluripotent Stem Cells Based On Bioinformatics Methods

Posted on:2022-10-25Degree:MasterType:Thesis
Country:ChinaCandidate:F L GaoFull Text:PDF
GTID:2480306524482314Subject:Biophysics
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Traditionally,stem cells are mainly embryonic stem cells(ES)as the source of medical stem cells.However,in addition to the immune rejection that may be caused by different organisms,there are also ethical issues in the use of ES.Therefore,another type of induced pluripotent stem cell(i PSc)with similar characteristics to ES came into being.i PSc is the introduction of specific transcription factors(TF)into differentiated somatic cells to transform them into pluripotent cells.Although the current i PSc research has made progress,people still need to further explore the induction mechanism of i PSc.In this paper,three somatic cell reprogramming processes of blood,skin and urine undergo significant changes during the i PSc process to explore the mechanism of i PSc production,and to predict the TF and mi RNA involved in the regulation of the reprogramming process.This research provides clues for the further development of a safer and more efficient reprogramming system.This paper uses bioinformatics methods to analyze the RNA-Seq data of the above three somatic cells and i PSc from these three somatic cells,and obtain the gene expression matrix through upstream analysis.Then it is divided into three groups according to the source of somatic cells: Bi vs B(source of blood cells),Fi vs F(source of skin layer fibers)and Ui vs U(source of urine cells),and then the reprogramming process of the three groups of cells Carry out a preliminary screening of differential genes,and use the selected candidate differential genes to construct a protein interaction network.Differential genes were screened out based on the degree of candidate differential gene interaction in the protein interaction network.Next,based on the regulatory relationship between TF,m RNA and mi RNA in molecular biology,the bioinformatics database is used to predict the three mi RNAs and TFs related to the reprogramming process of somatic cells,and use the three different genes related to somatic cells.,To analyze and discuss the reliability of predicted mi RNA and TF.Finally,this paper screened a total of 51 differential genes related to i PSc induction,and predicted 5 mi RNAs related to i PSc induction and 41 TFs related to i PSc induction.Among them,has-let-7c-5p and has-let-7a-5p are i PSc-related mi RNAs that have been proven by previous studies,and POU5F1,NANOG,SOX2,and MYC are 4transcription factors that have been proven to be related to i PSc.The biological processes and pathways of differential gene enrichment in the three somatic cell reprogramming processes are compared,and the specificity and commonality of the three somatic cell reprogramming are analyzed and compared.In addition,it was found that LIN28 A protein,OPRM1 protein,the inhibitors of SPP1 and the inhibitors of CDH1,respectively,may promote the successful induction of i PSc.Among them,LIN28 A is a transcription factor that has been verified by predecessors.The work in this paper has reference value for revealing the conversion mechanism of i PSc,and provides new clues for the development of a safer and more efficient iPSc induction system.
Keywords/Search Tags:Induced pluripotent stem cells, cell reprogramming, differential analysis, microRNA, transcription factor
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