Ectopic transgenic expression of NKX2.2 induces differentiation of adult pancreatic progenitors and mediates islet regeneration

被引：11

作者：

Chen, Shuyuan ^{[1
]}

Shimoda, Masayuki ^{[1
,2
]}

Chen, Jiaxi ^{[1
]}

Matsumoto, Shinichi ^{[1
,2
]}

Grayburn, Paul A. ^{[1
,3
]}

机构：

[1] Baylor Res Inst, Dallas, TX USA

[2] Baylor Res Inst, Ft Worth, TX USA

[3] Baylor Univ, Med Ctr, Dept Internal Med, Div Cardiol,Baylor Heart & Vasc Inst, Dallas, TX USA

来源：

CELL CYCLE | 2012年 / 11卷 / 08期

关键词：

islet regeneration; diabetes; pancreatic progenitors; differentiation; proliferation; NKX2.2; piggyBac transposon; ultrasound target microbubble destruction; TO-MESENCHYMAL TRANSITION; BETA-CELLS; IN-VIVO; PRECURSOR CELLS; TRANSPOSON IFP2; MOUSE PANCREAS; GENE-THERAPY; INSULIN; IDENTIFICATION; EFFICIENT;

D O I：

10.4161/cc.19928

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

To pursue islet regeneration in situ in adult pancreas with a diabetic animal model, we used ultrasound targeted microbubble destruction (UTMD) to deliver islet transcription factor genes to the pancreas of STZ-treated rats, specifically using a piggyBac transposon gene delivery system for long-term transgene expression of Nkx2.2 in STZ rat pancreas. Our results show that Nkx2.2 gene induced robust proliferation and differentiation of adult pancreatic progenitors. Our high-resolution confocal images precisely displayed how one single pancreatic progenitor cell differentiated into islets-like clusters and, further, into mature islets with normal morphology in situ in postnatal pancreas. Nkx2.2 targeted to the pancreas by UTMD induces pancreatic progenitor cell proliferation and differentiation with subsequent islet regeneration and cure of STZ-induced diabetes for three months.

引用

页码：1544 / 1553

页数：10

共 30 条

[1]

Cooperative Transcriptional Regulation of the Essential Pancreatic Islet Gene NeuroD1 (Beta2) by Nkx2.2 and Neurogenin 3 [J].