title: In vitro transdifferentiation of human peripheral blood mononuclear cells to photoreceptor-like cells.
abstract: Direct reprogramming is a promising, simple and low-cost approach to generate target cells from somatic cells without using induced pluripotent stem cells. Recently, peripheral blood mononuclear cells (PBMCs) have attracted considerable attention as a somatic cell source for reprogramming. As a cell source, PBMCs have an advantage over dermal fibroblasts with respect to the ease of collecting tissues. Based on our studies involving generation of photosensitive photoreceptor cells from human iris cells and human dermal fibroblasts by transduction of photoreceptor-related transcription factors via retrovirus vectors, we transduced these transcription factors into PBMCs via Sendai virus vectors. We found that retinal disease-related genes were efficiently detected in CRX-transduced cells, most of which are crucial to photoreceptor functions. In functional studies, a light-induced inward current was detected in some CRX-transduced cells. Moreover, by modification of the culture conditions including additional transduction of RAX1 and NEUROD1, we found a greater variety of retinal disease-related genes than that observed in CRX-transduced PBMCs. These data suggest that CRX acts as a master control gene for reprogramming PBMCs into photoreceptor-like cells and that our induced photoreceptor-like cells might contribute to individualized drug screening and disease modeling of inherited retinal degeneration.
authors.affiliation: Visual Functions Section, Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Saitama 359-8555, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Komuta
authors.affiliation: Department of Physiology, Nippon Medical School, Sendagi, Bunkyo, Tokyo 113-8602, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Physiology, Nippon Medical School, Sendagi, Bunkyo, Tokyo 113-8602, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneda
authors.affiliation: ID Pharma Co. Ltd, Tsukuba, Ibaraki 300-2611, Japan.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Visual Functions Section, Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Saitama 359-8555, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Department of Vascular Medicine, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Department of Reproductive Biology, Center for Regenerative Medicine, National Institute for Child Health and Development, Okura, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Visual Functions Section, Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Saitama 359-8555, Japan seko-yuko@rehab.go.jp.
authors.forename: Yuko
authors.identifier: http://orcid.org/0000-0003-0933-8350
authors.initials: Y
authors.lastname: Seko
keywords: Direct reprogramming; Human peripheral blood mononuclear cell (PBMC); Photoreceptor; Retinitis pigmentosa