Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells

Satoru Yoshida, Miyuki Yasuda, Hideyuki Miyashita, Yoko Ogawa, Tetsu Yoshida, Yumi Matsuzaki, Kazuo Tsubota, Hideyuki Okano, Shigeto Shimmura

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Application of induced pluripotent stem (iPS) cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required. Methodology/Principal Findings: We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method) with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo. Conclusions/Significance: These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be cloned from iPS cells in order to produce polarized multilayer epithelial cell sheets.

Original languageEnglish
Article numbere28856
JournalPLoS One
Volume6
Issue number12
DOIs
Publication statusPublished - 2011 Dec 9

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Induced Pluripotent Stem Cells
Stem cells
stem cells
epithelial cells
Stem Cells
Epithelial Cells
mice
medicine
cells
Tissue
Feeder Cells
Cell Polarity
Preclinical Drug Evaluations
Inborn Genetic Diseases
Regenerative Medicine
cadherins
Differentiation Antigens
embryonic stem cells
genetic disorders
cornea

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells. / Yoshida, Satoru; Yasuda, Miyuki; Miyashita, Hideyuki; Ogawa, Yoko; Yoshida, Tetsu; Matsuzaki, Yumi; Tsubota, Kazuo; Okano, Hideyuki; Shimmura, Shigeto.

In: PLoS One, Vol. 6, No. 12, e28856, 09.12.2011.

Research output: Contribution to journalArticle

Yoshida, Satoru ; Yasuda, Miyuki ; Miyashita, Hideyuki ; Ogawa, Yoko ; Yoshida, Tetsu ; Matsuzaki, Yumi ; Tsubota, Kazuo ; Okano, Hideyuki ; Shimmura, Shigeto. / Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells. In: PLoS One. 2011 ; Vol. 6, No. 12.
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