In GenStorm our goal is to combine high resolution microscopy with molecular modeling techniques. With this multidisciplinary approach we aim to understand how genes are organized within the cell nucleus and how this affects their function. The project is coordinated by Victoria Neguembor (Cosma lab at CRG) and Pablo Dans (Orozco lab at IRBB).
Our work on PoSTAC (Polycistronic SunTAg modified CRISPR) has been published in Nucleic Acids Research.
PoSTAC is a gene visualisation tool that combines CRISPR/dCas9 with SunTag labeling and polycistronic vectors. PoSTAC enables live cell and super-resolution imaging of multiple genes with high spatiotemporal resolution and high sensitivity.
Neguembor et al. 2017 Nucleic Acids Research
Ruben Sebastian Perez, a master student in our lab, has got the second place in the “Tell it to your parents” contest organized by Sociedad Española de Bioquímica y Biología Molecular (SEBBM).
Master students and bachelor students had to make videos for the general audience, in which they explain different Research concepts in the simplest way possible.
Below you can get a link to Ruben’s video : “A decade of iPS cells”
Until now hepatocyte replication has been considered the main mechanism of liver regeneration after hepatectomy in mammals. We recently found that bone marrow cells can migrate into the liver upon resection and fuse with the hepatocytes. The derived hybrids proliferate and are essential for efficient liver regeneration, which is also predicted by mathematical modelling.
Pedone et al. Cell Reports. 2017 Jan 3;18(1):107-121.
How do cells interact with other cells? We discovered that mouse mesenchymal stem cells (MSCs) can either fuse and form heterokaryons (cells with 2 nuclei) with mouse embryonic stem cells (ESCs) or can be invaded by ESCs through the entotic process (when one cell enters into another cell). Upon entosis the nucleus of the ESCs is degraded, while heterokaryons convert into synkaryons (cells with one nucleus containing both parental chromosomes) through cell division. These mechanisms are controlled by the activity of cytoskeleton components. Overall these are two profoundly different outcomes of cell-to-cell interactions, which might be important for different biological processes.
Sottile F. et al., Scientific Reports 2016 Nov 9;6:36863.
Retinitis pigmentosa covers a group of rare genetic disorders that cause retinal degeneration due to a loss of photoreceptors, the specialized cell-sensitive neurons that enable eyesight. By transplanting Wnt-activated hematopoietic stem and progenitor cells (HSPCs) we demonstrated that Muller cells can be reprogrammed in vivo after fusion with HSPCs. The newly generated hybrids can differentiate in photoreceptors leading to partial retina regeneration and to a certain degree of functional rescue. Sanges D, Simonte G DiVicino U, Romo N, Pinilla I, Nicolás Farrés M and Cosma MP (2016). In vivo conversion of Müller glia into photoreceptors through cell fusion-mediated reprogramming. Journal of Clinical Investigation, Aug 1;126(8):3104-3116
Alvaro Castells, PhD student in our lab, has scored second in the RIN4’ (Research in 4 Minutes) competition. This contest, open to all doctorates in the UPF, aims to promote the communicative abilities of the doctorates students in the Pompeu Fabra University, in order to improve their scientific communication skills.
Alvaro won the second prize, valued in 600 euros, with his presentation “Using super resolution microscopy to study RNA”, which allowed him to win for second consecutive year the second position.
His presentation was centered on STORM (Stochastic Optical Reconstruction Microscopy) technique, which bypasses the resolution limit of conventional microscopy (200nm) and allows the study of different cellular processes in a previous unachieved resolution.
Our paper on Parkinson’s disease therapy is in press in EBioMedicine (http://www.ebiomedicine.com/article/S2352-3964(16)30151-7/abstract), a new online journal supported by Cell press and Lancet. A definitive therapy for Parkinson’s disease is not available. In this work, we transplanted hematopoietic stem and progenitor cells into the substantia nigra of brains of two different mouse models of Parkinson’s disease. These transplanted cells fused with neurons and glial cells of the recipient mice. Four weeks after transplantation, the hybrids acquired features of mature astroglia, secreted Wnt1, and functionally ameliorated dopaminergic neuron loss. Current cell therapy approaches are being pursued in the striatum with the aim to increase dopamine levels. Here we show that the loss of dopaminergic neurons can be protected against by direct actions in the substantia nigra.
Altarche-Xifro W, Di Vicino U, Muñoz-Martin MI, Bové J, Vila M and Cosma MP (2016). Functional rescue of dopaminergic neuron loss in Parkinson’s disease mice after transplantation of hematopoietic stem and progenitor cells, EBioMedicine, in press.