Differentiated human stem cells resemble fetal, not adult, β cells

被引：248

作者：

Hrvatin, Sinisa ^{[1
]}

O'Donnell, Charles W. ^{[1
,3
]}

Deng, Francis ^{[1
]}

Millman, Jeffrey R. ^{[1
]}

Pagliuca, Felicia Walton ^{[1
]}

DiIorio, Philip ^{[4
]}

Rezania, Alireza ^{[5
]}

Gifford, David K. ^{[3
]}

Melton, Douglas A. ^{[1
,2
]}

机构：

[1] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[2] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA

[3] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[4] Univ Massachusetts, Sch Med, Diabet Ctr Excellence, Worcester, MA 01605 USA

[5] Janssen Res & Dev LLC, BetaL Venture, Raritan, NJ 08869 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 08期

基金：

美国国家卫生研究院;

关键词：

transcriptional profiling; differentiation; beta cells; MARIS; ISLET-LIKE CLUSTERS; EXPRESSION ANALYSIS; GENE-EXPRESSION; HUMAN ES; GLUCOSE; GENERATION; MATURATION; PAX4;

D O I：

10.1073/pnas.1400709111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic beta cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS+) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS+ cells and (ii) hPSC-derived INS+ (hPSC-INS+) cells more closely resemble human fetal beta cells than adult beta cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS+ cells and true beta cells and provides a catalog of genes whose manipulation may convert hPSC-INS+ cells into functional beta cells.

引用

页码：3038 / 3043

页数：6

共 59 条

[1]

Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells [J].