The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing Cells
The use of pancreatic β-cells differentiated from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a promising strategy in cell therapy. Pancreatic β-cell development is regulated by the sequential expression of a molecular network of transcription factors. In this experiment, we...
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doaj-5671109d41714378a5371335e07c0e972020-11-25T03:24:48ZengSAGE PublishingCell Transplantation0963-68971555-38922013-01-012210.3727/096368912X653057The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing CellsHuiming Xu0Kam Sze Tsang1Juliana C. N. Chan2Ping Yuan3Rongrong Fan4Hideaki Kaneto5Gang Xu6Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, ChinaLi Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, ChinaLi Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, ChinaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, ChinaDepartment of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, JapanLi Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, ChinaThe use of pancreatic β-cells differentiated from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a promising strategy in cell therapy. Pancreatic β-cell development is regulated by the sequential expression of a molecular network of transcription factors. In this experiment, we adopted a three-step differentiation protocol to differentiate mES (mouse ES) cells into insulin-secreting cells and overexpressed transcription factors by adenoviral vectors at various combinations at different time of differentiation. We found that the coexpression of Pdx1 and MafA with either Ngn3 or NeuroD, especially at the final stage of the three-step differentiation, significantly increased the differentiation efficiency. It also increased the glucose-stimulated insulin and C-peptide secretion in insulin-secreting cells derived from mES cells compared to the control green fluorescent protein (GFP) vector-transduced group. For the first time, we have demonstrated that the coexpression of Pdx1 and MafA during a specific time window of development can act synergistically with either Ngn3 or NeuroD to promote the differentiation of mES cells into insulin-secreting cells.https://doi.org/10.3727/096368912X653057 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huiming Xu Kam Sze Tsang Juliana C. N. Chan Ping Yuan Rongrong Fan Hideaki Kaneto Gang Xu |
spellingShingle |
Huiming Xu Kam Sze Tsang Juliana C. N. Chan Ping Yuan Rongrong Fan Hideaki Kaneto Gang Xu The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing Cells Cell Transplantation |
author_facet |
Huiming Xu Kam Sze Tsang Juliana C. N. Chan Ping Yuan Rongrong Fan Hideaki Kaneto Gang Xu |
author_sort |
Huiming Xu |
title |
The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing Cells |
title_short |
The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing Cells |
title_full |
The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing Cells |
title_fullStr |
The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing Cells |
title_full_unstemmed |
The Combined Expression of and with Either or Improves the Differentiation Efficiency of Mouse Embryonic Stem Cells into Insulin-Producing Cells |
title_sort |
combined expression of and with either or improves the differentiation efficiency of mouse embryonic stem cells into insulin-producing cells |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2013-01-01 |
description |
The use of pancreatic β-cells differentiated from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a promising strategy in cell therapy. Pancreatic β-cell development is regulated by the sequential expression of a molecular network of transcription factors. In this experiment, we adopted a three-step differentiation protocol to differentiate mES (mouse ES) cells into insulin-secreting cells and overexpressed transcription factors by adenoviral vectors at various combinations at different time of differentiation. We found that the coexpression of Pdx1 and MafA with either Ngn3 or NeuroD, especially at the final stage of the three-step differentiation, significantly increased the differentiation efficiency. It also increased the glucose-stimulated insulin and C-peptide secretion in insulin-secreting cells derived from mES cells compared to the control green fluorescent protein (GFP) vector-transduced group. For the first time, we have demonstrated that the coexpression of Pdx1 and MafA during a specific time window of development can act synergistically with either Ngn3 or NeuroD to promote the differentiation of mES cells into insulin-secreting cells. |
url |
https://doi.org/10.3727/096368912X653057 |
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