Investigating cone photoreceptor development using patient-derived NRL null retinal organoids.

Basic-Leucine Zipper Transcription Factors / deficiency Case-Control Studies Cell Differentiation / genetics Cells, Cultured Cellular Reprogramming / physiology Eye Diseases, Hereditary / genetics Eye Proteins / genetics Fetus / pathology Gene Expression Profiling Humans Induced Pluripotent Stem Cells / physiology Nerve Regeneration / genetics Neurogenesis / genetics Organoids / pathology Primary Cell Culture / methods Retina / pathology Retinal Cone Photoreceptor Cells / physiology Retinal Degeneration / genetics Retinitis Pigmentosa / genetics Transcriptome Vision Disorders / genetics

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
21 02 2020
Historique:
received: 28 08 2019
accepted: 21 01 2020
entrez: 22 2 2020
pubmed: 23 2 2020
medline: 22 6 2021
Statut: epublish

Résumé

Photoreceptor loss is a leading cause of blindness, but mechanisms underlying photoreceptor degeneration are not well understood. Treatment strategies would benefit from improved understanding of gene-expression patterns directing photoreceptor development, as many genes are implicated in both development and degeneration. Neural retina leucine zipper (NRL) is critical for rod photoreceptor genesis and degeneration, with NRL mutations known to cause enhanced S-cone syndrome and retinitis pigmentosa. While murine Nrl loss has been characterized, studies of human NRL can identify important insights for human retinal development and disease. We utilized iPSC organoid models of retinal development to molecularly define developmental alterations in a human model of NRL loss. Consistent with the function of NRL in rod fate specification, human retinal organoids lacking NRL develop S-opsin dominant photoreceptor populations. We report generation of two distinct S-opsin expressing populations in NRL null retinal organoids and identify MEF2C as a candidate regulator of cone development.

Identifiants

DOI: 10.1038/s42003-020-0808-5 PMID: 32081919 PMC: PMC7035245
pubmed: 32081919
doi: 10.1038/s42003-020-0808-5
pii: 10.1038/s42003-020-0808-5
pmc: PMC7035245
doi:

Substances chimiques

Basic-Leucine Zipper Transcription Factors 0
Eye Proteins 0
NRL protein, human 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

Pagination

82

Subventions

Organisme : NEI NIH HHS
ID : R01 EY021218
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007814
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY001765
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY012910
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY014104
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090256
Pays : United States

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Auteurs

Alyssa Kallman (A)

Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

Elizabeth E Capowski (EE)

Waisman Center, University of Wisconsin-Madison, Madison, USA.
ORCID: 0000-0002-8204-5434

Jie Wang (J)

Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, USA.
ORCID: 0000-0002-7491-7001

Aniruddha M Kaushik (AM)

Department of Mechanical Engineering, Johns Hopkins University, Baltimore, USA.

Alex D Jansen (AD)

Waisman Center, University of Wisconsin-Madison, Madison, USA.

Kimberly L Edwards (KL)

Waisman Center, University of Wisconsin-Madison, Madison, USA.

Liben Chen (L)

Department of Mechanical Engineering, Johns Hopkins University, Baltimore, USA.

Cynthia A Berlinicke (CA)

Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, USA.

M Joseph Phillips (M)

Waisman Center, University of Wisconsin-Madison, Madison, USA.
McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, USA.

Eric A Pierce (EA)

Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Boston, USA.

Jiang Qian (J)

Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, USA.

Tza-Huei Wang (TH)

Department of Mechanical Engineering, Johns Hopkins University, Baltimore, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, USA.

David M Gamm (DM)

Waisman Center, University of Wisconsin-Madison, Madison, USA. dgamm@wisc.edu.
McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, USA. dgamm@wisc.edu.
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, USA. dgamm@wisc.edu.

Donald J Zack (DJ)

Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. donzack@gmail.com.
Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, USA. donzack@gmail.com.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, USA. donzack@gmail.com.
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, USA. donzack@gmail.com.
ORCID: 0000-0002-7966-1973

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Investigating cone photoreceptor development...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Investigating cone photoreceptor development...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Investigating cone photoreceptor development...
questionsmedicales.fr › Cellules › Cellules cultivées › Investigating cone photoreceptor development...
questionsmedicales.fr › Phénomènes génétiques › Reprogrammation cellulaire › Investigating cone photoreceptor development...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies héréditaires de l'oeil › Investigating cone photoreceptor development...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de l'oeil › Investigating cone photoreceptor development...
questionsmedicales.fr › Structures de l'embryon › Foetus › Investigating cone photoreceptor development...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Investigating cone photoreceptor development...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Investigating cone photoreceptor development...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › Investigating cone photoreceptor development...
questionsmedicales.fr › Phénomènes biologiques › Régénération › Régénération nerveuse › Investigating cone photoreceptor development...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Neurogenèse › Investigating cone photoreceptor development...
questionsmedicales.fr › Tissus › Organoïdes › Investigating cone photoreceptor development...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › Investigating cone photoreceptor development...
questionsmedicales.fr › Organes des sens › Oeil › Rétine › Investigating cone photoreceptor development...
questionsmedicales.fr › Cellules › Neurones › Neurones afférents › Cellules réceptrices sensorielles › Cellules photoréceptrices › Cellules photoréceptrices de vertébré › Cellules photoréceptrices en cône de la rétine › Investigating cone photoreceptor development...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Dégénérescence de la rétine › Investigating cone photoreceptor development...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies héréditaires de l'oeil › Rétinite pigmentaire › Investigating cone photoreceptor development...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Investigating cone photoreceptor development...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles sensitifs › Troubles de la vision › Investigating cone photoreceptor development...