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

Taku Kaitsuka, Kohei Kobayashi, Wakako Otsuka, Takuya Kubo, Farzana Hakim, Fan Yan Wei, Nobuaki Shiraki, Shoen Kume, Kazuhito Tomizawa

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    Abstract

    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 phos-phorylated 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.

    Original languageEnglish
    Pages (from-to)C573-C582
    JournalAmerican Journal of Physiology - Cell Physiology
    Volume312
    Issue number5
    DOIs
    Publication statusPublished - May 2017

    Keywords

    • Definitive endoderm
    • Differentiation
    • ERK
    • Embryonic stem cell
    • Erythropoietin

    ASJC Scopus subject areas

    • Physiology
    • Cell Biology

    Fingerprint

    Dive into the research topics of 'Erythropoietin facilitates definitive endodermal differentiation of mouse embryonic stem cells via activation of ERK signaling'. Together they form a unique fingerprint.

    Cite this