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In a new study, researchers from the Free University of Brussels in Belgium and the University of Cambridge in the UK identified the role of the key gene Mesp1 in the earliest stages of cardiovascular cell line age separation.
findings may help to better understand congenital heart defects.
related findings were published online January 25, 2018 in the journal Science with the headline "Defining the st of the step of the life of the cardiovascular lineage by-single cell RNA-seq".
heart is the first organ formed during development and consists of four regions (the ventricle and the atrium) that contain cells that perform special functions: beating myocardial cells ensure pumped blood activity; vascular cells form the endoscope of the blood vessel; and pacipacing cells regulate the heartbeat.
severe heart malformations occur unless heart progenitor cells are produced at the right time, migrated to the right location, and differentiated into the right cell type.
in humans, these heart malformations are considered congenital heart disease and are the most common cause of severe birth defects in newborns.
previous studies have shown that many heart progenitor cells are produced by different groups of cells that express the Mesp1 gene.
However, it is still unclear how these different cardiac progenitor cells can be distinguished at the molecular level, and which molecular mechanisms promote the production of a particular heart region, or cardiac cell lineage.
In the new study, a team led by Professor C?dric Blanpain of the Stem Cell and Cancer Laboratory at the Free University of Brussels and Professor Berthold G?tgens of the University of Cambridge used single-cell molecular spectra and lineage tracking techniques to identify the earliest stages of mesp1's separation of cardiovascular cell lines.
Fabienne Lescroart and his colleagues isolated the cells expressing Mesp1 at different stages of embryonic development and performed a single-cell transcription group analysis of these early cardiac progeny cells to identify the molecular characteristics associated with the region and cell type identity of the heart's progeny cells.
they confirmed that different groups of heart progenitor cells have very different molecular characteristics.
to determine the role of transcription factor Mesp1 in regulating the heterogeneity of cardiovascular differentiation procedures and early cardiovascular progenitor cells, they also performed single-cell molecular spectral analysis of these early protocells in the absence of Mesp1.
these experiments show that Mesp1 is necessary to withdraw the plhomine state and activate the cardiovascular gene expression procedure.
by conducting bioinformatics analyses, the researchers identified different cell populations in these early expression Mesp1 cardiovascular progeny cells that corresponded to targeted birth of different heart cell lineages and heart regions, and identified molecular characteristics associated with early lineage restrictions and cardiac region separation.
although cardiovascular progenitor cells have not yet differentiated, these new results suggest that they are "ready" or pre-designated to produce cardiomyocytes or vascular cells.
the researchers found that at this early stage of development, these different cell populations were also produced at different points in time and existed at specific sites.
finally, the researchers identified the earliest branching points between the heart cell lineage and the vascular cell lineage, and confirmed that Notch1 was a marker of early progenitor cells that directed the vascular cell lineage during early embryonic development.
understanding of the molecular characteristics associated with early cardiovascular cell lineage and cardiac regions will be critical to the design of new strategies to guide cardiovascular protocellular identity to heart cell identity or vascular cell identity from different heart regions, and the resulting cells can be used to treat heart disease. "Future studies will need to determine whether the early cell lineage separation patterns identified in this study control the formation of different cell lineages in different organs and tissues," commented Professor C?dric Blanpain,
.
also important, determine whether the molecular characteristics revealed by this study play a role in congenital heart malformations, and whether they can also be used to promote cardiovascular progenitor cell differentiation into specific cell lineages, which may have important implications for improved cell therapy for heart repair. "Our new findings rely heavily on recent technological innovations that allow us to determine the genetic activity spectrum of individual cells," said Professor Bertie Gottgens,
.
not only can we study microcell populations that we could not have studied before, but we can also use computers to divide individual cells into cell subgroups or cell types based on their genetic activity spectrum.
as Branpain points out, from these newly discovered gene activity spectrums, we can identify new candidate heart genes that could be used to develop new therapies for heart repair.
" References: Fabine Lescroart, Xiaonan Wang, Xionghui Lin et al. Defining the sage step of cardiovascularlineby by single-cell RNA-seq.science, published online: 25 Jan 2018, doi: 10.1126/science.aao4174.