Sep 22, 2017

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

Scientific Reports
Nathan LawlorMichael L Stitzel

Abstract

Alpha TC1 (αTC1) and Beta-TC-6 (βTC6) 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 αTC1 and βTC6 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 αTC1/βTC6 cis-regulatory elements. αTC1/βTC6 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 αTC1/βTC6 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 αTC1/βTC6 and primary islet...Continue Reading

  • References
  • Citations2

References

  • We're still populating references for this paper, please check back later.

Mentioned in this Paper

Diabetes Mellitus, Non-Insulin-Dependent
Transcriptional Regulation
Structure of Beta Cell of Islet
Genome
Genomic Profile
Transcription, Genetic
Genomic Stability
Total cholesterol
XCL1
JM 2820

Related Feeds

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Arushi VarshneyMichael L Stitzel
Proceedings of the National Academy of Sciences of the United States of America
Stephen C J ParkerNISC Comparative Sequencing Program Authors
© 2020 Meta ULC. All rights reserved