Bioinformatics Analysis Of Molecular Mechanism Of The Expansion Of Hematopoietic Stem Cell Transduced By HOXB4/HOXC4

Purpose:Common differentially expressed genes with the same expression pattern in HOXB4-and HOXC4-treated CD34+cells(HOXB4&HOXC4.DEGs)were screened out.Additionally,functional enrichment analysis were performed,and transcription regulatory network were constructed for exploring TFs corresponding to these DEGs.We aimed to give a systematic perspective to elucidate the key mechanism and identify the potential HOX downstream effectors involved in HSCs expansion.Methods:1.The microarray data GSE24379 was down loaded from Gene Expression Omnibus(GEO)database,including total 12 human CD34+ hematopoietic cells with GFP-,HOXB4-,or HOXC4-transduced MS-5 cells respectively;2.All the array data were preprocessed using LOESS normalization.We then identified DEGs in CD34+ cells co-cultured with MS-5/HOXB4 and co-cultured MS-5/HOXC4 using limma in R package,respectively;3.Protein-protein interaction network was constructed and functional modules analysis was performed;4.Pathway enrichment analysis was performed using the Database for Annotation Visualization and Integrated Discovery;5.Transcription regulatory network was constructed to screen transcription factors corresponding to HOXB4&HOXC4.DEGs.Results:1.We identified a total of 547 DEGs(478 up-and 69 down-regulated)in CD34+ /MS-5/HOXB4 vs.CD34+/MS-5/GFP group and 718 DEGs(642 up-and 76 down-regulated)in CD34+/MS-5/HOXC4 vs.CD34+/MS-5/GFP group.The results showed that the numbers of up-regulated genes were significantly more than down-regulated genes no matter in HOXB4-treated or HOXC4-treated CD34+cells;2.Tumor protein p53(TP53)with the highest degrees was hub node in PPI network;3.Cyclin B1(CCNB1)was hub nodes in Cluster 1;4.MYC associated factor X(MAX)were important TFs with higher degrees;5.MYC,TP53 and CCNB1 were significantly enriched in cell cycle.Conclusion:1.MYC protein is confirmed to induce cell cycle progression and apoptosis via dimerization with MAX;2.MYC,MAX,TP53 and CCNB1 may be crucial HOXB4/HOXC4 downstream molecules potentially involved in HSCs expansion;3.HOXB4 and HOXC4 homeoprotein could display positive effects on expansion of human HSCs via regulating these genes.