IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The role of the Glucocorticoid Receptor in pancreatic progenitor cell differentiation and beta cell genesis
Autor/es:
VALLIER, L.; CHHATRIWALA, M.; RODRÍGUEZ SEGUÍ, S. A.; TRABA, S.A.; PECCI, A.
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigacion Clínica (SAIC); 2016
Institución organizadora:
Sociedad Argentina de Investigacion Clínica (SAIC)
Resumen:
p { margin-bottom: 0.1in; direction: ltr; line-height: 120%; text-align: left; }a:link { color: rgb(0, 0, 255); }The invitro production offunctional beta cells for transplantation in type 1 diabetic patientsis a long-standing goal to achieve, which would allow the suppressionof insulin administration. Current differentiation protocols toderive beta cells from human pluripotent stem cells (hPSCs)artificially mimic the cell signaling events that occur during fetaldevelopment, and involve manipulation of signaling pathways that areknown to play key and stage-specific roles during pancreas growth anddifferentiation. Thus, gaining insights into the mechanisms by whichnovel pathways control this process might significantly impact thisfield of research. Previous studies have shown that theglucocorticoid receptor (GR) signaling pathway plays an importantrole in the generation of an appropriate number of beta cells toaccomplish an accurate glycemic control in adults, although theunderlying molecular mechanisms still remain largely unexplored. Wehave recently reported the construction of genomic cisregulatory maps in human pancreatic islets and in the human embryonicpancreas based on ChIP-seq and RNA-seq experiments. In the lattercase we used human pancreatic buds that were dissected from 6-7 wpcembryos and cells from a matched differentiation stage that were invitro derived fromhPSCs. Our analyses led to the discovery that TEAD and YAP areimportant gene expression regulators that in the embryonic pancreasare in charge of maintaining the MPC phenotype. Further analysis ofthis resource shows that a subset of the genes that are highlyexpressed in MPCs could be downregulated upon activation of the GRpathway. Using in vitromouse and human models of pancreas development, our current effortsare focused in understanding how glucocorticoids affect the MPC geneexpression program.