Fellows-seminar

#IDIBELLfellows: Gisele Priscila Soares de Aguiar & Adrián Holguín Horcajo

Gisele Priscila Soares de Aguiar & Adrián Holguín Horcajo

Neurodevelopmental Disorders group; Pancreas regeneration: pancreatic progenitors and their niche group

29/10/2024

15:00-16:00

McClintock Room & online

Abstract

Deciphering the role of extracellular matrix towards amyotrophic lateral sclerosis pathogenesis
Gisele Priscila Soares de Aguiar – Neurodevelopmental Disorders group
Amyotrophic lateral sclerosis (ALS) is an untreatable and progressive degenerative disease that affects motor neurons, leading to muscle weakness, atrophy, and paralysis. We hypothesize that the extracellular matrix (ECM) has an important role in ALS pathogenesis that has been underestimated because of the intrinsic properties of ECM proteins, which technically complicates their identification and experimental analysis. We first decellularized ECM (dECM) from spinal cords of the SOD1G93A ALS mouse model and demonstrated differences in their biophysical properties respect to wild type (WT) mice. We also adapted a biochemical decellularization protocol coupled to mass spectrometry (MS) analysis to provide a high coverage of ECM protein profiles, known as matrisome, of the spinal cord of the SOD1G93A mice. We observed differences in the spinal cord matrisome of SOD1G93Avs. WT animals that were further validated through western blot and transcriptomic metanalysis. The use of SOD1G93A dECM or pharmacological and genetic modification of the expression of identified ECM targets produced alterations in cell survival, morphology, and electrophysiological properties in human iPSC-deriveed motor neurons. Lastly, ECM proteins identified to be at higher levels in SOD1G93A matrisome were found to be increased in the CSF of ALS patients. Therefore, our results represent the first deep ALS matrisome map, elucidating cell extrinsic effectors of ALS pathogenesis and potential new biomarkers.

Are Peribiliary Glands and Pancreatic Ductal Glands the same entity? Unravelling a putative common adult pancreatic progenitor cell population outside the pancreas
Adrián Holguín Horcajo – Pancreas regeneration: pancreatic progenitors and their niche group
Peribiliary Glands (PBGs) are outpouch structures that emerge from the Common Biliary Duct (CBD), around the ampulla of Vater, the cystic duct and the common hepatic duct. Previous studies described the inside of these structures as a location of a progenitor cell population with regenerative capacities. Likewise, inside the pancreas and associated to the biggest pancreatic ducts, there are similar structures, although smaller in size, than those located in the Common Biliary Duct, called Pancreatic Ductal Glands (PDGs). These PDGs are not well defined, but it is known that this structure can be the niche of adult pancreatic progenitors. Therefore, our main goal is to study the similarities between both structures and to understand whether these compartment harbour adult progenitor cells. In order to do that, we performed Single Nuclei RNA-Seq from the CBD and the Main Pancreatic Duct (MPD), identifying a similar population in PBGs and PDGs that shared some common markers, obtaining cells similar to an intestinal stem cells. Our omics studies identified surface markers to isolate the newly identified populations to perform in vitro organoid cultures to further assess the capacity of these cells to differentiate into endocrine (β-cells) and exocrine pancreatic lineages

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