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Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.
Parikh, Bhav Harshad; Blakeley, Paul; Regha, Kakkad; Liu, Zengping; Yang, Binxia; Bhargava, Mayuri; Wong, Daniel Soo Lin; Tan, Queenie Shu Woon; Wong, Claudine See Wei; Wang, Hao Fei; Al-Mubaarak, Abdurrahmaan; Chou, Chai; Cheung, Chui Ming Gemmy; Lim, Kah Leong; Barathi, Veluchamy Amutha; Hunziker, Walter; Lingam, Gopal; Hu, Tim Xiaoming; Su, Xinyi.
Afiliación
  • Parikh BH; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Blakeley P; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Regha K; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
  • Liu Z; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Yang B; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
  • Bhargava M; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Wong DSL; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
  • Tan QSW; Singapore Eye Research Institute, Singapore 169856, Singapore.
  • Wong CSW; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Wang HF; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Al-Mubaarak A; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
  • Chou C; Department of Ophthalmology, National University Hospital, Singapore 119074, Singapore.
  • Cheung CMG; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
  • Lim KL; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Barathi VA; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Hunziker W; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Lingam G; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
  • Hu TX; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
  • Su X; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
Proc Natl Acad Sci U S A ; 120(26): e2214842120, 2023 06 27.
Article en En | MEDLINE | ID: mdl-37339216
Transplantation of stem cell-derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation, and fate specification of transplanted RPE cells. To address this, we transplanted stem cell-derived RPE into the subretinal space of immunocompetent rabbits for 1 mo and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory-inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation toward the native adult human RPE state in all transplanted RPE, regardless of stem cell resource. Gene regulatory network analysis suggests that tripartite transcription factors (FOS, JUND, and MAFF) may be specifically activated in posttransplanted RPE cells, to regulate canonical RPE signature gene expression crucial for supporting host photoreceptor function, and to regulate prosurvival genes required for transplanted RPE's adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transcriptoma / Degeneración Macular Límite: Adult / Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2023 Tipo del documento: Article País de afiliación: Singapur

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transcriptoma / Degeneración Macular Límite: Adult / Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2023 Tipo del documento: Article País de afiliación: Singapur