scholarly journals Erythropoietin facilitates definitive endodermal differentiation of mouse embryonic stem cells via activation of ERK signaling

2017 ◽  
Vol 312 (5) ◽  
pp. C573-C582 ◽  
Author(s):  
Taku Kaitsuka ◽  
Kohei Kobayashi ◽  
Wakako Otsuka ◽  
Takuya Kubo ◽  
Farzana Hakim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Early Stage ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Definitive Endoderm ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Pancreatic Differentiation

Artificially generated pancreatic β-cells from pluripotent stem cells are expected for cell replacement therapy for type 1 diabetes. Several strategies are adopted to direct pluripotent stem cells toward pancreatic differentiation. However, a standard differentiation method for clinical application has not been established. It is important to develop more effective and safer methods for generating pancreatic β-cells without toxic or mutagenic chemicals. In the present study, we screened several endogenous factors involved in organ development to identify the factor, which induced the efficiency of pancreatic differentiation and found that treatment with erythropoietin (EPO) facilitated the differentiation of mouse embryonic stem cells (ESCs) into definitive endoderm. At an early stage of differentiation, EPO treatment significantly increased Sox17 gene expression, as a marker of the definitive endoderm. Contrary to the canonical function of EPO, it did not affect the levels of phosphorylated JAK2 and STAT5, but stimulated the phosphorylation of ERK1/2 and Akt. The MEK inhibitor U0126 significantly inhibited EPO-induced Sox17 expression. The differentiation of ESCs into definitive endoderm is an important step for the differentiation into pancreatic and other endodermal lineages. This study suggests a possible role of EPO in embryonic endodermal development and a new agent for directing the differentiation into endodermal lineages like pancreatic β-cells.

Definitive endoderm: a key step in coaxing human embryonic stem cells into transplantable β-cells

2008 ◽  
Vol 36 (3) ◽  
pp. 272-275 ◽  
Author(s):  
Henrik Semb
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Insulin Pump ◽  
Embryonic Stem ◽  
Definitive Endoderm ◽  
Attractive Alternative ◽  
Β Cells ◽  
Number Of Patients

Using the Edmonton protocol, a number of patients with Type 1 diabetes mellitus have remained insulin-independent for prolonged periods of time. In spite of this success, transplantation of islets from cadaver donors will remain a therapy for very few patients owing to a lack of donors. Thus, if cell therapy should be widely available, it will require an unlimited source of cells to serve as a ‘biological’ insulin pump. At this time, the development of β-cells from hESCs (human embryonic stem cells) has emerged as the most attractive alternative. It is envisioned that ultimate success of an in vitro approach to programme hESCs into β-cells will depend on the ability, at least to a certain degree, to sequentially reproduce the individual steps that characterizes normal β-cell ontogenesis during fetal pancreatic development, including definitive endoderm from which all gastrointestinal organs, including the pancreas, originate. In the present article, differentiation of hESCs into putative definitive endodermal cell types is reviewed.

scholarly journals Differentiation patterns of mouse embryonic stem cells and induced pluripotent stem cells into neurons

2014 ◽  
Vol 68 (3) ◽  
pp. 409-417 ◽  
Author(s):  
Mai Nakamura ◽  
Yu Kamishibahara ◽  
Ayako Kitazawa ◽  
Hideo Kawaguchi ◽  
Norio Shimizu
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Induced Pluripotent

Inducing Embryonic Stem Cells to Differentiate into Pancreatic β Cells by a Novel Three-Step Approach with Activin A and All-TransRetinoic Acid

Stem Cells ◽  
2005 ◽  
Vol 23 (5) ◽  
pp. 656-662 ◽  
Author(s):  
Yan Shi ◽  
Lingling Hou ◽  
Fuchou Tang ◽  
Wei Jiang ◽  
Peigang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Activin A ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Dual Inhibition of BMP and WNT Signals Promotes Pancreatic Differentiation from Human Pluripotent Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Mengtian Tan ◽  
Lai Jiang ◽  
Yinglei Li ◽  
Wei Jiang
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Beta Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Signal Pathways ◽  
Pancreatic Differentiation ◽  
Dual Inhibition ◽  
Induced Pluripotent ◽  
Wnt Signal

Pathological or functional loss of pancreatic beta cells is the cause of diabetes. Understanding how signaling pathways regulate pancreatic lineage and searching for combinations of signal modulators to promote pancreatic differentiation will definitely facilitate the robust generation of functional beta cells for curing hyperglycemia. In this study, we first tested the effect of several potent BMP inhibitors on pancreatic differentiation using human embryonic stem cells. Next, we examined the endodermal lineage bias upon potent BMP inhibitor treatment and further checked the crosstalk between signal pathways governing endodermal lineage determination. Furthermore, we improved current pancreatic differentiation system based on the signaling pathway study. Finally, we used human-induced pluripotent stem cells to validate our finding. We found BMP inhibitors indeed not only blocked hepatic lineage but also impeded intestinal lineage from human definitive endoderm unexpectedly. Signaling pathway analysis indicated potent BMP inhibitor resulted in the decrease of WNT signal activity and inhibition of WNT could contribute to the improved pancreatic differentiation. Herein, we combined the dual inhibition of BMP and WNT signaling and greatly enhanced human pancreatic progenitor differentiation as well as beta cell generation from both embryonic stem cells and induced pluripotent stem cells. Conclusively, our present work identified the crosstalk between the BMP and WNT signal pathways during human endoderm patterning and pancreas specification, and provided an improved in vitro pancreatic directed differentiation protocol from human pluripotent stem cells.

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