Gene catalog for differentiating human pluripotent stem cells (hPSCs) into mature, insulin-producing pancreatic β cells

Abstract The efficient generation of pancreatic β cells from human pluripotent stem cells may allow us to study their biological characteristics and use them for the treatment of type I diabetes. The protocol we present in the study provides an efficient method for producing β cells using either human embryonic stem cells or human induced pluripotent stem cells as the starting material.

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Generation of β cells from human pluripotent stem cells: Are we there yet?

Annals of the New York Academy of Sciences ◽

10.1111/nyas.12369 ◽

2014 ◽

Vol 1311 (1) ◽

pp. 124-137 ◽

Cited By ~ 33

Author(s):

Jacqueline V. Schiesser ◽

James M. Wells

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Human Pluripotent Stem Cells ◽

Β Cells

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

AJP Cell Physiology ◽

10.1152/ajpcell.00071.2016 ◽

2017 ◽

Vol 312 (5) ◽

pp. C573-C582 ◽

Cited By ~ 1

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.

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Drug-Induced Naïve iPS Cells Exhibit Better Performance than Primed iPS Cells with Respect to the Ability to Differentiate into Pancreatic β-Cell Lineage

Journal of Clinical Medicine ◽

10.3390/jcm9092838 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2838

Author(s):

Yuki Kiyokawa ◽

Masahiro Sato ◽

Hirofumi Noguchi ◽

Emi Inada ◽

Yoko Iwase ◽

...

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Cell Lineage ◽

Ips Cells ◽

Embryoid Bodies ◽

Specific Marker ◽

Β Cells ◽

Β Cell ◽

Pancreatic Β Cells

Pluripotent stem cells are classified as naïve and primed cells, based on their in vitro growth characteristics and potential to differentiate into various types of cells. Human-induced pluripotent stem cells (iPSCs, also known as epiblast stem cells [EpiSCs]) have limited capacity to differentiate and are slightly more differentiated than naïve stem cells (NSCs). Although there are several in vitro protocols that allow iPSCs to differentiate into pancreatic lineage, data concerning generation of β-cells from these iPSCs are limited. Based on the pluripotentiality of NSCs, it was hypothesized that NSCs can differentiate into pancreatic β-cells when placed under an appropriate differentiation induction condition. We examined whether NSCs can be efficiently induced to form potentially pancreatic β cells after being subjected to an in vitro protocol. Several colonies resembling in vitro-produced β-cell foci, with β-cell-specific marker expression, were observed when NSC-derived embryoid bodies (EBs) were induced to differentiate into β-cell lineage. Conversely, EpiSC-derived EBs failed to form such foci in vitro. Intrapancreatic grafting of the in vitro-formed β-cell foci into nude mice (BALB/c-nu/nu) generated a cell mass containing insulin-producing cells (IPCs), without noticeable tumorigenesis. These NSCs can be used as a promising resource for curing type 1 diabetes.

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