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- Publisher Website: 10.1073/PNAS.2214842120
- Scopus: eid_2-s2.0-85163922719
- PMID: 37339216
- WOS: WOS:001031821300007
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Article: Single-cell transcriptomics reveals maturation of transplanted stem cell–derived retinal pigment epithelial cells toward native state
Title | Single-cell transcriptomics reveals maturation of transplanted stem cell–derived retinal pigment epithelial cells toward native state |
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Authors | Parikh, Bhav HarshadBlakeley, PaulRegha, KakkadLiu, ZengpingYang, BinxiaBhargava, MayuriWong, Daniel Soo LinTan, Queenie Shu WoonWong, Claudine See WeiWang, Hao FeiAl-Mubaarak, AbdurrahmaanChou, ChaiCheung, Chui Ming GemmyLim, Kah LeongBarathi, Veluchamy AmuthaHunziker, WalterLingam, GopalHu, Tim XiaomingSu, Xinyi |
Keywords | cell transplantation pluripotent stem cell retinal pigment epithelium transcriptome |
Issue Date | 2023 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2023, v. 120, n. 26, article no. e2214842120 How to Cite? |
Abstract | 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. |
Persistent Identifier | http://hdl.handle.net/10722/335903 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Parikh, Bhav Harshad | - |
dc.contributor.author | Blakeley, Paul | - |
dc.contributor.author | Regha, Kakkad | - |
dc.contributor.author | Liu, Zengping | - |
dc.contributor.author | Yang, Binxia | - |
dc.contributor.author | Bhargava, Mayuri | - |
dc.contributor.author | Wong, Daniel Soo Lin | - |
dc.contributor.author | Tan, Queenie Shu Woon | - |
dc.contributor.author | Wong, Claudine See Wei | - |
dc.contributor.author | Wang, Hao Fei | - |
dc.contributor.author | Al-Mubaarak, Abdurrahmaan | - |
dc.contributor.author | Chou, Chai | - |
dc.contributor.author | Cheung, Chui Ming Gemmy | - |
dc.contributor.author | Lim, Kah Leong | - |
dc.contributor.author | Barathi, Veluchamy Amutha | - |
dc.contributor.author | Hunziker, Walter | - |
dc.contributor.author | Lingam, Gopal | - |
dc.contributor.author | Hu, Tim Xiaoming | - |
dc.contributor.author | Su, Xinyi | - |
dc.date.accessioned | 2023-12-28T08:49:37Z | - |
dc.date.available | 2023-12-28T08:49:37Z | - |
dc.date.issued | 2023 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2023, v. 120, n. 26, article no. e2214842120 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/335903 | - |
dc.description.abstract | 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. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | cell transplantation | - |
dc.subject | pluripotent stem cell | - |
dc.subject | retinal pigment epithelium | - |
dc.subject | transcriptome | - |
dc.title | Single-cell transcriptomics reveals maturation of transplanted stem cell–derived retinal pigment epithelial cells toward native state | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1073/PNAS.2214842120 | - |
dc.identifier.pmid | 37339216 | - |
dc.identifier.scopus | eid_2-s2.0-85163922719 | - |
dc.identifier.volume | 120 | - |
dc.identifier.issue | 26 | - |
dc.identifier.spage | article no. e2214842120 | - |
dc.identifier.epage | article no. e2214842120 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:001031821300007 | - |