A Chromatin Basis for Cell Lineage and Disease Risk in the Human Pancreas

Cell Systems
H Efsun ArdaSeung K Kim

Abstract

Understanding the genomic logic that underlies cellular diversity and developmental potential in the human pancreas will accelerate the growth of cell replacement therapies and reveal genetic risk mechanisms in diabetes. Here, we identified and characterized thousands of chromatin regions governing cell-specific gene regulation in human pancreatic endocrine and exocrine lineages, including islet β cells, α cells, duct, and acinar cells. Our findings have captured cellular ontogenies at the chromatin level, identified lineage-specific regulators potentially acting on these sites, and uncovered hallmarks of regulatory plasticity between cell types that suggest mechanisms to regenerate β cells from pancreatic endocrine or exocrine cells. Our work shows that disease risk variants related to pancreas are significantly enriched in these regulatory regions and reveals previously unrecognized links between endocrine and exocrine pancreas in diabetes risk.

Citations

Nov 23, 2019·Current Diabetes Reports·Inês Cebola
Jul 23, 2020·Nature Metabolism·Krissie TellezSeung K Kim
Sep 11, 2019·Molecular Metabolism·Nathan Lawlor, Michael L Stitzel
Jan 16, 2021·Genes & Development·Romina J BevacquaSeung K Kim
Feb 5, 2021·Nature·Direna Alonso-CurbeloScott W Lowe
Feb 2, 2021·Genome Medicine·Evangelina López de MaturanaNúria Malats
Apr 30, 2020·Trends in Biochemical Sciences·Ruth NussinovHyunbum Jang
Apr 13, 2021·Endocrine Reviews·John T WalkerAlvin C Powers

❮ Previous
Next ❯

Related Concepts

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.

BioHub - Researcher Network

The Chan-Zuckerberg Biohub aims to support the fundamental research and develop the technologies that will enable physicians to cure, prevent, or manage all diseases in our childrens' lifetimes. The CZ Biohub brings together researchers from UC Berkeley, Stanford, and UCSF. Find the latest research from the CZ Biohub researcher network here.