Research Highlight #1: Inhibition of cell cycle regulators alters the EHT
Posted by AlessandroDonada, on 12 May 2020
Hello everyone! My name is Alessandro, I am a postdoc in love with science, stem cells and blood! I am also a big fan of the Node, The Company of Biologists generously granted me a travel grant back in 2016, that allowed me to discover the beautiful Cambridge (the old one). As the lockdown starts to ease a bit around the world, I have decided to start a little writing workout: I will try to regularly post a highlight of science that grabbed my attention, as a paper or preprint. Feedback is more than welcome, as are suggestions. I hope you will enjoy my writings, you can find me also on Twitter (@BioRugby)!
Highlight #1: Inhibition of cell cycle regulators alters the EHT efficiency of endothelial-to-haematopoietic transition
Endothelial-to-Haematopoietic Transition (EHT) is the key mechanism behind the formation of the first haematopoietic stem cells. Albeit first described in the mid-80s, we still do not understand some of the cellular mechanism that regulates it. In their preprint, Canu and colleagues used human pluripotent stem cells to characterize the EHT. Extensive use of single-cell transcriptomics revealed the existence of multiple endothelial and haematopoietic populations; one of the latter was able to generate myeloid and erythroid colonies, revealing a certain multipotency. Interestingly, the transcriptomic analysis revealed different cell cycle activity between populations, prompting the authors to investigate the cell cycle impact on EHT. Slowing down cell cycle progression disrupted the occurrence of EHT, increasing the proportion of endothelial cells without modifying their viability. Moreover, a similar phenotype was observed by inhibiting cyclin-dependent kinase 1 (CDK1) and CDK4/6, which suggests that the EHT disruption is not caused by the decreased proliferation of endothelial cells. Taken together, this manuscript proves a major impact on differentiation for CDKs, beyond their canonical role as cell cycle regulators. The proposed link between cell cycle and differentiation has major implications on our understanding of haematopoietic development. The authors successfully proved it in a robust and human-relevant experimental system, combining single-cell transcriptomics, flow cytometry and functional assays. It will be very intriguing to delve further into the molecular intricacies of EHT, to reveal their impact on this fascinating developmental transition.
Canu G et al. “Analysis of Endothelial-to-Haematopoietic Transition at the Single-Cell Level identifies Cell Cycle Regulation as a Driver of Differentiation”.
doi: https://doi.org/10.1101/2020.04.03.023762.
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Relates to doi:10.1038/nature22326, p. 439, May 25, 2017, vol 545. Induced pluripotency route has oncogenic issues?