The basic instructions for cell functioning are written in its genetic sequence, DNA, which is practically identical in all cells of the body, although its interpretation varies greatly depending on the tissue where it is found, its physiological conditions and the stage of development. This variability is a result of gene expression regulation, which selects which particular DNA fragments are transcribed into mRNA and also controls the maturation of this mRNA. In the second case, post-transcriptional regulation, one of the essential mechanisms is alternative polyadenylation (PAA), which consists of defining which DNA fragments are included in the final mRNA. The terminal regions of the mRNA do not normally affect the function of related proteins, but they do affect their regulation and localization. This makes PAA a key mechanism for cell differentiation and development and response to environmental stimuli. In fact, alterations in these PAA patterns have been linked to altered gene expression and the appearance of tumors.
To better understand this phenomenon, transcriptomics tools that analyze the mRNA in each individual cell are necessary. In this sense, a research group from IDIBELL and the UB has just presented SCALPEL, a tool to quantify and characterize single-cell mRNAs with a significantly higher sensitivity and specificity compared to existing methods.
New cell populations found thanks to SCALPEL
In the publication in Nature Communications they explain that, thanks to this tool, researchers have been able to discover new cell populations that were undetectable when only gene expression data were observed. An example is RS6 cells, a new population of round spermatids involved in flagellum elongation and spermatid differentiation, an essential step for sperm formation. Before, these cells had been described morphologically, but they had never been able to be characterized molecularly.
As Dr. Mireya Plass, head of the Gene expression regulation research group at IDIBELL and leader of the study, explains, “We have seen that, if we analyze the cells involved in spermatogenesis using SCALPEL, we find hundreds of genes that give rise to several mRNA isoforms, the amount of which varies according to the phase of the spermatogenesis process. This is how we have molecularly identified RS6 cells, which appear at a very specific time to carry out a specific function: the elongation of the spermatid flagellum. These very specific temporal photographs cannot be obtained only from genetic sequencing, it is necessary to create transcriptomics tools such as SCALPEL.”
Work like this shows that further exploration of post-transcriptional gene regulation in individual cells in different species and tissues is needed to understand the development and differentiation of each cell type with better temporal resolution. In the future, this knowledge could be applied to the study and treatment of complex diseases such as cancer or neurodegenerative diseases such as Alzheimer’s.
The Bellvitge Biomedical Research Institute (IDIBELL) is a research center established in 2004 specialized in cancer, neuroscience, translational medicine, and regenerative medicine. It counts on a team of more than 1.500 professionals who, from 73 research groups, publish more than 1.400 scientific articles per year. IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona, and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).