Alpha TC1 and Beta-TC-6 genomic profiling uncovers both shared and distinct transcriptional regulatory features with their primary islet counterparts

Alpha TC1 (alpha TC1) and Beta-TC-6 (beta TC6) mouse islet cell lines are cellular models of islet (dys) function and type 2 diabetes (T2D). However, genomic characteristics of these cells, and their similarities to primary islet alpha and beta cells, are undefined. Here, we report the epigenomic (ATAC-seq) and transcriptomic (RNA-seq) landscapes of alpha TC1 and beta TC6 cells. Each cell type exhibits hallmarks of its primary islet cell counterpart including cell-specific expression of beta (e.g., Pdx1) and alpha (e.g., Arx) cell transcription factors (TFs), and enrichment of binding motifs for these TFs in alpha TC1/beta TC6 cis-regulatory elements. alpha TC1/beta TC6 transcriptomes overlap significantly with the transcriptomes of primary mouse/human alpha and beta cells. Our data further indicate that ATAC-seq detects cell-specific regulatory elements for cell types comprising >= 20% of a mixed cell population. We identified alpha TC1/beta TC6 cis-regulatory elements orthologous to those containing type 2 diabetes (T2D)-associated SNPs in human islets for 33 loci, suggesting these cells' utility to dissect T2D molecular genetics in these regions. Together, these maps provide important insights into the conserved regulatory architecture between alpha TC1/beta TC6 and primary islet cells that can be leveraged in functional (epi) genomic approaches to dissect the genetic and molecular factors controlling islet cell identity and function.