Nicotinamide Promotes Formation of Retinal Organoids From Human Pluripotent Stem Cells

BMP pathway induced pluripotent stem cells neuroectoderm nicotinamide retinal organoids

Journal

Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935

Informations de publication

Date de publication:
2022
Historique:
received: 17 02 2022
accepted: 25 05 2022
entrez: 5 7 2022
pubmed: 6 7 2022
medline: 6 7 2022
Statut: epublish

Résumé

Retinal organoids (ROs) derived from human pluripotent stem cells (hPSCs) recapitulate key features of retinogenesis and provide a promising platform to study retinal development and disease in a human context. Although multiple protocols are currently in use, hPSCs exhibit tremendous variability in differentiation efficiency, with some cell lines consistently yielding few or even no ROs, limiting their utility in research. We report here that early nicotinamide (NAM) treatment significantly improves RO yield across 8 hPSC lines from different donors, including some that would otherwise fail to generate a meaningful number of ROs. NAM treatment promotes neural commitment of hPSCs at the expense of non-neural ectodermal cell fate, which in turn increases eye field progenitor generation. Further analysis suggests that this effect is partially mediated through inhibition of BMP signaling. Our data encourage a broader use of human ROs for disease modeling applications that require the use of multiple patient-specific cell lines.

Identifiants

pubmed: 35783089
doi: 10.3389/fncel.2022.878351
pmc: PMC9247291
doi:

Types de publication

Journal Article

Langues

eng

Pagination

878351

Informations de copyright

Copyright © 2022 Regent, Batz, Kelley, Gieser, Swaroop, Chen and Li.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Florian Regent (F)

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Zachary Batz (Z)

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Ryan A Kelley (RA)

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Linn Gieser (L)

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Anand Swaroop (A)

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Holly Y Chen (HY)

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Tiansen Li (T)

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Classifications MeSH