近日，美国费城儿童医院Paul Gadue及其研究团队发现，一个非编码区域可影响胰腺发育不全。相关论文于2020年5月21日在线发表在《细胞—干细胞》杂志上。

Title: A Non-Coding Disease Modifier of Pancreatic Agenesis Identified by Genetic Correction in a Patient-Derived iPSC Line

Author: Siddharth Kishore, Elisa De Franco, Fabian L. Cardenas-Diaz, Lisa R. Letourneau-Freiberg, May Sanyoura, Catherine Osorio-Quintero, Deborah L. French, Siri Atma W. Greeley, Andrew T. Hattersley, Paul Gadue

Issue&Volume: 2020-05-21

Abstract: GATA6 is a critical regulator of pancreatic development, with heterozygous mutationsin this transcription factor being the most common cause of pancreatic agenesis. Tostudy the variability in disease phenotype among individuals harboring these mutations,a patient-induced pluripotent stem cell model was used. Interestingly, GATA6 proteinexpression remained depressed in pancreatic progenitor cells even after correctionof the coding mutation. Screening the regulatory regions of the GATA6 gene in these patient cells and 32 additional agenesis patients revealed a higherminor allele frequency of a SNP 3′ of the GATA6 coding sequence. Introduction of this minor allele SNP by genome editing confirmedits functionality in depressing GATA6 expression and the efficiency of pancreas differentiation.This work highlights a possible genetic modifier contributing to pancreatic agenesisand demonstrates the usefulness of using patient-induced pluripotent stem cells fortargeted discovery and validation of non-coding gene variants affecting gene expressionand disease penetrance.

DOI: 10.1016/j.stem.2020.05.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30199-5