CRX Expression in Pluripotent Stem Cell-Derived Photoreceptors Marks a Transplantable Subpopulation of Early Cones.
Animals
Cell Differentiation
/ genetics
Cell Lineage
/ genetics
Humans
Induced Pluripotent Stem Cells
/ transplantation
Mice
Organoids
/ transplantation
Pluripotent Stem Cells
/ transplantation
Retina
/ growth & development
Retinal Cone Photoreceptor Cells
/ cytology
Retinal Degeneration
/ genetics
Retinal Rod Photoreceptor Cells
/ transplantation
Transcriptome
/ genetics
CRX
Pde6brd1 mice
Photoreceptors
Pluripotent stem cells
Single cell RNA-seq
Subretinal transplantation
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
23
06
2018
revised:
05
11
2018
accepted:
03
12
2018
pubmed:
27
1
2019
medline:
28
4
2020
entrez:
26
1
2019
Statut:
ppublish
Résumé
Death of photoreceptors is a common cause of age-related and inherited retinal dystrophies, and thus their replenishment from renewable stem cell sources is a highly desirable therapeutic goal. Human pluripotent stem cells provide a useful cell source in view of their limitless self-renewal capacity and potential to not only differentiate into cells of the retina but also self-organize into tissue with structure akin to the human retina as part of three-dimensional retinal organoids. Photoreceptor precursors have been isolated from differentiating human pluripotent stem cells through application of cell surface markers or fluorescent reporter approaches and shown to have a similar transcriptome to fetal photoreceptors. In this study, we investigated the transcriptional profile of CRX-expressing photoreceptor precursors derived from human pluripotent stem cells and their engraftment capacity in an animal model of retinitis pigmentosa (Pde6brd1), which is characterized by rapid photoreceptor degeneration. Single cell RNA-Seq analysis revealed the presence of a dominant cell cluster comprising 72% of the cells, which displayed the hallmarks of early cone photoreceptor expression. When transplanted subretinally into the Pde6brd1 mice, the CRX
Identifiants
pubmed: 30681766
doi: 10.1002/stem.2974
pmc: PMC6519156
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
609-622Subventions
Organisme : Medical Research Council
ID : MR/N015037/1
Pays : United Kingdom
Organisme : MRC
ID : MC_PC_15030
Pays : International
Organisme : Medical Research Council
ID : MC_UP_1501/2
Pays : United Kingdom
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/C016106/1
Pays : United Kingdom
Organisme : MRC
ID : MR/M008886/1
Pays : International
Organisme : Medical Research Council
ID : MC_PC_15030
Pays : United Kingdom
Organisme : BBSRC
ID : #BB/I02333X/1
Pays : International
Organisme : Medical Research Council
ID : MR/M008886/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00015/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R011338/1
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019.
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