DOI: 10.1038/s41556-019-0318-1
In the meticulous process of hematopoiesis – the creation of blood cellular components from haematopoietic stem cells (HSCs) – the regulation of HSC self-renewal and differentiation is crucial for maintaining a balanced blood system. The precise mechanisms governing these regulatory pathways, however, had remained largely obscure, until the recent illuminating research, conducted by a team from Columbia University Medical Center and the Weizmann Institute of Science, brought forward new insights into the stage-specific requirements for N6-methyladenosine (m6A) modification in HSC differentiation.
Lead researchers, Heather Lee, Suying Bao, Yingzhi Qian, Shay Geula, and their colleagues have entered the spotlight of the scientific community with their publication in Nature Cell Biology. By incorporating sophisticated genetic tools and sequencing analysis, the team identified the crucial role of Mettl3 – an m6A methyltransferase – in the regulation of gene expression during the early stages of HSC differentiation.
Research Overview
The recent study aimed to decode the role of Mettl3 by deleting the gene in early, mid, and late hematopoietic progenitors. The results were indicative of a stage-specific requirement for Mettl3, where its deletion in early progenitors led to widespread changes in gene expression and halted differentiation, while deletion at later stages showed a lesser impact.
The importance of Mettl3 was further substantiated by its influence on the expression of the c-Myc proto-oncogene – a critical factor in cell cycle progression and metabolism. A closer look at RNA sequencing data revealed that m6A modifications controlled by Mettl3 affected the regulation of c-Myc mRNA expression.
This groundbreaking research sheds light on the importance of epigenetic control within stem cell differentiation and encourages further exploration of Mettl3 as a potential therapeutic target for blood-related disorders where the differentiation process is compromised.
References
1. Rossi L, et al. (2012). Less is more: unveiling the functional core of hematopoietic stem cells through knockout mice. Cell Stem Cell. doi:10.1016/j.stem.2012.08.006
2. Morrison SJ & Scadden DT. (2014). The bone marrow niche for haematopoietic stem cells. Nature. doi:10.1038/nature12984
3. Desrosiers R, et al. (1974). Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. PNAS. doi:10.1073/pnas.71.10.3971
4. Meyer KD & Jaffrey SR. (2014). The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol. doi:10.1038/nrm3785
5. Geula S, et al. (2015). m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science. doi:10.1126/science.1261417
Keywords
1. Mettl3 in Haematopoiesis
2. Epigenetic regulation of HSCs
3. m6A modification stem cells
4. Hematopoietic differentiation Mettl3
5. Blood stem cell gene expression
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