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Spivakov sets up Functional Gene Control group at the MRC LMS

 2 November 2018   Research News

Dr Mikhail Spivakov has recently joined the MRC LMS to lead the Functional Gene Control group within the Epigenetics section.

Mikhail’s area of research interest is regulatory genomics, investigating the control of gene expression. At the LMS his research group will focus on how specific types of DNA regions termed gene enhancers integrate information from within and outside the cell that is needed to decide which genes will be switched on and off. The group aim to answer questions such as ‘what is the logic underlying the regulatory function of gene enhancers?’ and ‘how is information from external signals processed in the cell nucleus to result in specific instructions for gene control?’

Mikhail has joined the MRC LMS from the Babraham Institute in Cambridge, where he established his research group back in 2012. He shared his thoughts on joining the LMS:

Confetti Sca1-stained plaque image

Plasticity of vascular smooth muscle cells (VSMCs) implicates them in cardiovascular disease progression. Here the authors use lineage tracing and single cell RNA sequencing to identify a rare population of healthy Sca1+ VSMCs which upregulate an activated transcriptional signature shared by disease-associated cells. Image shows Sca1-expressing lineage-labelled VSMCs inside an arterial atherosclerotic plaque.

“This is a fantastic environment for our group. The institute has a great concentration of expertise in topics I care deeply about, including epigenetics, gene regulation and cell-environment interactions. Beyond that, links with Imperial facilitate partnerships across disciplines, which are also very relevant for our group. I look forward to exciting and productive collaborations with LMS and Imperial scientists.”

An element of Mikhail’s work at Babraham was a collaborative project with Dr Helle Jørgensen, a group leader at the University of Cambridge’s Division of Cardiovascular Medicine, which was published on 1 November in Nature Communications. This mouse study has shown that it may be possible to detect the early signs of atherosclerosis, which leads to blocked arteries, by looking at how cells in the blood vessels change their function. The findings could lead to earlier diagnosis and new treatments for atherosclerosis in the future.

Mikhail research

Plasticity of vascular smooth muscle cells (VSMCs) implicates them in cardiovascular disease progression. Here the authors use lineage tracing and single cell RNA sequencing to identify a rare population of healthy Sca1+ VSMCs which upregulate an activated transcriptional signature shared by disease-associated cells. Image shows a tSNE plot with expression of this transcriptional signature in VSMCs from atherosclerotic plaques.

Atherosclerosis is one of the most prominent cardiovascular diseases in the UK. It can lead to serious cardiovascular diseases such as heart attacks and stroke, due to the blockages formed in the blood vessels. Coronary heart disease, the progressed form of atherosclerosis, is responsible for over 66,000 deaths in the UK each year [1].

Researchers focused their study on a distinct population of cells that line the blood vessels. The main function of these vascular smooth muscle cells is pumping blood through the body, but they are also involved in ‘patching up’ injuries in the blood vessels. Overzealous switching of these cells from the ‘pumping’ to the ‘repair’ mode can lead to atherosclerosis, resulting in the formation of ‘plaques’ in the blood vessels that block the arteries.

Spivakov’s and Jørgensen’s groups have caught a tiny number of vascular muscle cells in mouse blood vessels in the act of switching and described their molecular properties. This research has been made possible by an innovative methodology known as single-cell RNA-sequencing, which makes it possible to track the activity of most genes in the genome in hundreds to thousands of individual vascular muscle cells.

“Identifying the populations of cells involved in inflammatory response in the blood vessels is the crucial first step that enables further functional studies in this system. We can now ask what proteins and what DNA elements are involved in switching the cells between the two modes, and what exactly goes wrong with the switching process in disease”, says Mikhail.

The full publication “Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels” can be read here: https://www.nature.com/articles/s41467-018-06891-x. The research was funded by the British Heart Foundation and UK Research and Innovation.

For further information about Mikhail Spivakov’s Functional Gene Control group: https://lms.mrc.ac.uk/research-group/functional-gene-control/. You can also follow Mikhail on Twitter @mikhailspivakov.

References:
Dobnikar, L, Taylor, AL et al. Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy vessels. Nature Communications; 1 Nov 2018; DOI: 10.1038/s41467-018-06891

[1] BHF statistics about coronary heart disease https://www.bhf.org.uk/what-we-do/our-research/heart-statistics

This article was written by Angel Thomas, Scout Davies and Jenna Stevens-Smith.