Derivation of Human Differential Photoreceptor-like Cells from the Iris by Defined Combinations of CRX, RX and NEUROD

Autor: Makoto Kaneda, Akihiro Umezawa, Noriyuki Azuma, Yuuki Noshiro, Kei Nakatani, Hideyuki Okano, Yoshitaka Miyagawa, Yuko Seko, Reiko Kurokawa
Rok vydání: 2012
Předmět:
Opsin
Anatomy and Physiology
genetic structures
Cellular differentiation
Iris
lcsh:Medicine
Cell Fate Determination
Photoreceptor cell
chemistry.chemical_compound
Molecular Cell Biology
Basic Helix-Loop-Helix Transcription Factors
lcsh:Science
NeuroD
Genetics
Multidisciplinary
biology
Stem Cells
Gene Expression Regulation
Developmental
Cell Differentiation
Sensory Systems
Cell biology
medicine.anatomical_structure
Somatic Cells
Rhodopsin
Medicine
Retinal Disorders
Cellular Types
Research Article
Biotechnology
Photoreceptor Cells
Vertebrate
Visual phototransduction
Transcriptional Activation
Light Signal Transduction
Cell Potency
Bioengineering
Nerve Tissue Proteins
Complementary and Alternative Medicine
medicine
Humans
Inherited Eye Disorders
Eye Proteins
Biology
Homeodomain Proteins
Retina
Tissue Engineering
lcsh:R
Rod Opsins
Retinal
Molecular Development
eye diseases
Ophthalmology
chemistry
Macular Disorders
Trans-Activators
biology.protein
lcsh:Q
sense organs
Developmental Biology
Neuroscience
Transcription Factors
Zdroj: PLoS ONE, Vol 7, Iss 4, p e35611 (2012)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0035611
Popis: 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.
Databáze: OpenAIRE
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