Induction of intermediate mesoderm by retinoic acid receptor signaling from differentiating mouse embryonic stem cells

Oeda, Shiho, Hayashi, Yohei, Chan, Techuan, Takasato, Minoru, Aihara, Yuko, Okabayashi, Koji, Ohnuma, Kiyoshi and Asashima, Makoto (2013) Induction of intermediate mesoderm by retinoic acid receptor signaling from differentiating mouse embryonic stem cells. International Journal of Developmental Biology, 57 383-389. doi:10.1387/ijdb.130058ma


Author Oeda, Shiho
Hayashi, Yohei
Chan, Techuan
Takasato, Minoru
Aihara, Yuko
Okabayashi, Koji
Ohnuma, Kiyoshi
Asashima, Makoto
Title Induction of intermediate mesoderm by retinoic acid receptor signaling from differentiating mouse embryonic stem cells
Journal name International Journal of Developmental Biology   Check publisher's open access policy
ISSN 0214-6282
1696-3547
Publication date 2013-07-03
Sub-type Article (original research)
DOI 10.1387/ijdb.130058ma
Open Access Status
Volume 57
Start page 383
End page 389
Total pages 7
Editor Makoto Asashima
Place of publication Bilbao, Spain
Publisher Servicio Editorial, Universidad del Pais Vasco
Language eng
Formatted abstract
Renal lineages including kidney are derived from intermediate mesoderm, which are differentiated from a subset of caudal undifferentiated mesoderm. The inductive mechanisms of mammalian intermediate mesoderm and renal lineages are still poorly understood. Mouse embryonic stem cells (mESCs) can be a good in vitro model to reconstitute the developmental pathway of renal lineages and to analyze the mechanisms of the sequential differentiation. We examined the effects of Activin A and retinoic acid (RA) on the induction of intermediate mesoderm from mESCs under defined, serum-free, adherent, monolayer culture conditions. We measured the expression level of intermediate mesodermal marker genes and examined the developmental potential of the differentiated cells into kidney using an ex vivo transplantation assay. Adding Activin A followed by RA to mESC cultures induced the expression of marker genes and proteins for intermediate mesoderm, odd-skipped related 1 (Osr1) and Wilm’s Tumor 1 (Wt1). These differentiated cells integrated into laminin-positive tubular cells and Pax2-positive renal cells in cultured embryonic kidney explants. We demonstrated that intermediate mesodermal marker expression was also induced by RA receptor (RAR) agonist, but not by retinoid X receptor (RXR) agonists. Furthermore, the expression of these markers was decreased by RAR antagonists. We directed the differentiation of mESCs into intermediate mesoderm using Activin A and RA and revealed the role of RAR signaling in this differentiation. These methods and findings will improve our understanding of renal lineage development and could contribute to the regenerative medicine of kidney.
Keyword Kidney
Activin A
Odd-skipped related 1
Pax 2
Wilm’s tumor 1
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 03 Sep 2014, 11:58:08 EST by Minoru Takasato on behalf of Institute for Molecular Bioscience