Weighted gene co-expression network analysis reveals the hub genes and molecular mechanism of quiescence

Fecha de publicación: 20/01/2025
Fuente: PubMed "nature biotechnology"
3 Biotech. 2025 Feb;15(2):42. doi: 10.1007/s13205-024-04203-3. Epub 2025 Jan 15.ABSTRACTThe hematopoietic stem cell (HSC) continues their functional integrity and return to quiescence quickly even after inflammatory and other proliferative stress. The mechanism which is responsible for this highly regulatory process is not understood clearly. Previous results have shown that CD53 is noticeably upregulated in HSCs in response to a variety of stimuli. Gene expression profile using RNASeq data of HSCs from the bone marrow and spleen of CD53 knock out and their wild-type littermate had been deposited by Greenberg and co-authors, in GEO database, "GSE219050". They reported that knockout of CD53 promotes continued cell cycle. To identify key genes and specific processes are affected in absence of CD53, we applied weighted gene co-expression analysis. The results show that cyan module is correlated and dark red and light cyan are anti-correlated with CD53 loss. CDK1 is identified as more connected gene or hub gene in cyan module and it is upregulated in the absence of CD53. Likewise, hub genes from dark-red module are EP300, EGF, MCL1, LPL and IGF1R. The gene enrichment analysis depicts, two biological processes, MAPK cascade and Delta Notch signalling were suppressed. Similarly, the biological processes involved in light-cyan module are chromatin organisation and hub genes are Ehmt2, Ezh2, Kdm1a, Rbbp4, Esr1 and Mysm1. It uncovers the roles of CD53 in chromatin organisation, and MAPK cascade and Delta Notch signalling are the major contributors in quiescence mechanism. These findings might provide a new avenue in quiescence research.PMID:39829641 | PMC:PMC11735823 | DOI:10.1007/s13205-024-04203-3