The species origin of the cellular microenvironment influences markers of beta cell fate and function in EndoC-βH1 cells

• Published in: Experimental cell research Vol. 361; no. 2; pp. 284 - 291
• Main Authors: Jeffery, N., Richardson, S., Beall, C., Harries, L.W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.2017
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Beta-cells; Cell Communication - drug effects; Cell Line; Cellular Microenvironment - genetics; Diabetes; Extracellular Matrix - chemistry; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Gene Expression Regulation; Glucagon - genetics; Glucagon - metabolism; Glucose - pharmacology; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Insulin - genetics; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Mice; Microenvironment; Signal Transduction; Species Specificity; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Beta-cells; Diabetes; Microenvironment
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2017.10.028

Interaction between islet cell subtypes and the extracellular matrix influences beta-cell function in mammals. The tissue architecture of rodent islets is very different to that of human islets; cell-to-cell communication and interaction with the extracellular matrix may vary between species. In this work, we have compared the responses of the human EndoC-βH1 cell line to non-human and human-derived growth matrices in terms of growth morphology, gene expression and glucose-stimulated insulin secretion (GSIS). EndoC-βH1 cells demonstrated a greater tendency to form cell clusters when cultured in a human microenvironment and exhibited reduced alpha cell markers at the mRNA level; mean expression difference − 0.23 and − 0.51; p = 0.009 and 0.002 for the Aristaless-related homeobox (ARX) and Glucagon (GCG) genes respectively. No differences were noted in the protein expression of mature beta cell markers such as Pdx1 and NeuroD1 were noted in EndoC-βH1 cells grown in a human microenvironment but cells were however more sensitive to glucose (4.3-fold increase in insulin secretion following glucose challenge compared with a 1.9-fold increase in cells grown in a non-human microenvironment; p = 0.0003). Our data suggests that the tissue origin of the cellular microenvironment has effects on the function of EndoC-βH1 cells in vitro, and the use of a more human-like culture microenvironment may bring benefits in terms of increased physiological relevance. •The cellular microenvironment is important to beta-cell function.•Human derived culture reagents improve glucose sensitive insulin secretion in EndoC-βH1 cells.•A more human cellular microenvironment consolidates gene markers of beta-cell fate.