Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 12 2023
04 12 2023
Historique:
received:
26
05
2023
revised:
15
08
2023
accepted:
18
08
2023
medline:
21
9
2023
pubmed:
20
9
2023
entrez:
20
9
2023
Statut:
ppublish
Résumé
Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.
Identifiants
pubmed: 37728563
pii: 276285
doi: 10.1084/jem.20230913
pmc: PMC10510736
pii:
doi:
Substances chimiques
Biomarkers
0
Retinal Pigments
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NEI NIH HHS
ID : R01 EY032138
Pays : United States
Organisme : NEI NIH HHS
ID : U01 EY030581
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY022079
Pays : United States
Organisme : NIH HHS
ID : R01EY032138
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY029281
Pays : United States
Informations de copyright
© 2023 Farjood et al.
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