Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD.

Yuko Seko, Noriyuki Azuma, Makoto Kaneda, Kei Nakatani, Yoshitaka Miyagawa, Yuuki Noshiro, Reiko Kurokawa, Hideyuki Okano, Akihiro Umezawa

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Examples of direct differentiation by defined transcription factors have been provided for beta-cells, cardiomyocytes and neurons. In the human visual system, there are four kinds of photoreceptors in the retina. Neural retina and iris-pigmented epithelium (IPE) share a common developmental origin, leading us to test whether human iris cells could differentiate to retinal neurons. We here define the transcription factor combinations that can determine human photoreceptor cell fate. Expression of rhodopsin, blue opsin and green/red opsin in induced photoreceptor cells were dependent on combinations of transcription factors: A combination of CRX and NEUROD induced rhodopsin and blue opsin, but did not induce green opsin; a combination of CRX and RX induced blue opsin and green/red opsin, but did not induce rhodopsin. Phototransduction-related genes as well as opsin genes were up-regulated in those cells. Functional analysis; i.e. patch clamp recordings, clearly revealed that generated photoreceptor cells, induced by CRX, RX and NEUROD, responded to light. The response was an inward current instead of the typical outward current. These data suggest that photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. These findings contribute substantially to a major advance toward eventual cell-based therapy for retinal degenerative diseases.

Original languageEnglish
JournalPLoS One
Volume7
Issue number4
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

iris (eyes)
Photoreceptor Cells
opsin
Iris
photoreceptors
Rhodopsin
Transcription Factors
rhodopsin
Neurons
Retina
transcription factors
Genes
cells
Light Signal Transduction
Opsins
Retinal Neurons
Retinal Diseases
Functional analysis
Clamping devices
Cell- and Tissue-Based Therapy

ASJC Scopus subject areas

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

Cite this

Seko, Y., Azuma, N., Kaneda, M., Nakatani, K., Miyagawa, Y., Noshiro, Y., ... Umezawa, A. (2012). Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD. PLoS One, 7(4).

Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD. / Seko, Yuko; Azuma, Noriyuki; Kaneda, Makoto; Nakatani, Kei; Miyagawa, Yoshitaka; Noshiro, Yuuki; Kurokawa, Reiko; Okano, Hideyuki; Umezawa, Akihiro.

In: PLoS One, Vol. 7, No. 4, 2012.

Research output: Contribution to journalArticle

Seko, Y, Azuma, N, Kaneda, M, Nakatani, K, Miyagawa, Y, Noshiro, Y, Kurokawa, R, Okano, H & Umezawa, A 2012, 'Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD.', PLoS One, vol. 7, no. 4.
Seko, Yuko ; Azuma, Noriyuki ; Kaneda, Makoto ; Nakatani, Kei ; Miyagawa, Yoshitaka ; Noshiro, Yuuki ; Kurokawa, Reiko ; Okano, Hideyuki ; Umezawa, Akihiro. / Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD. In: PLoS One. 2012 ; Vol. 7, No. 4.
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