Apoorvha J P, Brindha S, Ganesan M, Roy Sujata
Department of Biotechnology, Rajalakshmi Engineering College, Thandalam, Chennai, 602105 India.
3 Biotech. 2025 Feb;15(2):42. doi: 10.1007/s13205-024-04203-3. Epub 2025 Jan 15.
The 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 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.
造血干细胞（HSC）即使在炎症和其他增殖应激后仍能保持其功能完整性，并迅速恢复静止状态。负责这一高度调控过程的机制尚不清楚。先前的结果表明，CD53在HSC中受到多种刺激后显著上调。Greenberg及其共同作者已将来自CD53基因敲除小鼠及其野生型同窝小鼠的骨髓和脾脏中HSC的RNAseq数据的基因表达谱存入GEO数据库“GSE219050”。他们报告说，CD53基因敲除会促进细胞周期的持续进行。为了确定在没有CD53的情况下受影响的关键基因和特定过程，我们应用了加权基因共表达分析。结果表明，青色模块与CD53缺失相关，深红色和浅青色模块与CD53缺失呈负相关。CDK1被确定为青色模块中连接性更强的基因或枢纽基因，在没有CD53的情况下上调。同样，深红色模块中的枢纽基因是EP300、EGF、MCL1、LPL和IGF1R。基因富集分析表明，有两个生物学过程，即MAPK级联反应和Delta Notch信号传导受到抑制。同样，浅青色模块中涉及的生物学过程是染色质组织，枢纽基因是Ehmt2、Ezh2、Kdm1a、Rbbp4、Esr1和Mysm1。它揭示了其在染色质组织中的作用，并且MAPK级联反应和Delta Notch信号传导是静止机制的主要贡献者。这些发现可能为静止研究提供一条新途径。
