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TrxG complex catalytic and non-catalytic activity play distinct roles in pancreas progenitor specification and differentiation (shDpy30 lentivirus treated spheres)

ABSTRACT: Purpose: To determine the genome-wide effect of Wdr5 and Dpy30 suppression on acinar, duct and endocrine gene activation during pancreas spheroid differentiation Methods: We adapted an ex vivo mouse E13.5 pancreas spheroid model of growth and differentiation (Sugiyama et al., 2013) and generated RNA-sequencing data from pooled shScramble, shWdr5 and shDpy30 spheroids. Results: We identified 1,744 genes whose expression was substantially impaired and 693 genes with increased expression in shWdr5-treated spheres compared to shScramble controls. In shDpy30-treated spheres, we identified no genes with impaired expression and only 2 genes with increased expression compared to shScramble controls. Genes expressed in pancreas progenitors were largely not altered by either Wdr5 or Dpy30 suppression. However, genes expressed in the endocrine (Gcg, Ins1, Ins2 and Neurog3) and acinar (Cpa1, Cpa2 and Amy2) lineages had dramatically reduced expression in shWdr5-treated spheres, but were unaffected by Dpy30 suppression. Conclusions: These data suggest that the co-activator activity of the TrxG complexes and not their methyltransferase activity, is required for acinar and endocrine cell gene activation in an ex vivo model of pancreas development.

ORGANISM(S): Mus musculus

PROVIDER: GSE134182 | GEO | 2019/07/12

REPOSITORIES: GEO

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Project description:deBack2012 - Lineage Specification in Pancreas Development This model of two neighbouring pancreas precursor cells, describes the exocrine versus endocrine lineage specification process. To account for the tissue scale patterns, this couplet model has been extended to hundreds of coupled cells. This model is described in the article: On the role of lateral stabilization during early patterning in the pancreas de Back W., Zhou JX, Brusch L J. R. Soc. Interface 6 February 2013 vol. 10 no. 79 20120766 Abstract: The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell–cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell–cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development. This model is hosted on BioModels Database and identified by: MODEL1211010000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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TrxG complex catalytic and non-catalytic activity play distinct roles in pancreas progenitor specification and differentiation (shDpy30 lentivirus treated spheres)

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