Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells

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Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells. / Mikhailova, Alexandra; Ilmarinen, Tanja; Uusitalo, Hannu; Skottman, Heli.

In: Stem Cell Reports, Vol. 2, No. 2, 11.02.2014, p. 219-231.

Research output: Contribution to journal › Article › Scientific › peer-review

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Mikhailova, Alexandra ; Ilmarinen, Tanja ; Uusitalo, Hannu ; Skottman, Heli. / Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells. In: Stem Cell Reports. 2014 ; Vol. 2, No. 2. pp. 219-231.

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@article{eb4a31cc0514422288c34c8111fefa99,

title = "Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells",

abstract = "Human induced pluripotent stem cells (hiPSCs) offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF) in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95{\%} of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.",

author = "Alexandra Mikhailova and Tanja Ilmarinen and Hannu Uusitalo and Heli Skottman",

year = "2014",

month = "2",

day = "11",

doi = "10.1016/j.stemcr.2013.12.014",

language = "English",

volume = "2",

pages = "219--231",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Elsevier",

number = "2",

}

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TY - JOUR

T1 - Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells

AU - Mikhailova, Alexandra

AU - Ilmarinen, Tanja

AU - Uusitalo, Hannu

AU - Skottman, Heli

PY - 2014/2/11

Y1 - 2014/2/11

N2 - Human induced pluripotent stem cells (hiPSCs) offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF) in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.

AB - Human induced pluripotent stem cells (hiPSCs) offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF) in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.

UR - http://www.scopus.com/inward/record.url?scp=84893769217&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2013.12.014

DO - 10.1016/j.stemcr.2013.12.014

M3 - Article

VL - 2

SP - 219

EP - 231

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 2

ER -

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