Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation.

Large-eyed model age-related macular degeneration cellular profiling and transcriptome cellular therapy clinical translation differentiation protocol dynamics human embryonic stem cell-derived retinal pigment epithelial cell retinal progenitor cells single-cell RNA sequencing subretinal injection

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
14 06 2022
Historique:
received: 27 03 2022
revised: 12 05 2022
accepted: 13 05 2022
entrez: 15 6 2022
pubmed: 16 6 2022
medline: 18 6 2022
Statut: ppublish

Résumé

Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) are a promising cell source to treat age-related macular degeneration (AMD). Despite several ongoing clinical studies, a detailed mapping of transient cellular states during in vitro differentiation has not been performed. Here, we conduct single-cell transcriptomic profiling of an hESC-RPE differentiation protocol that has been developed for clinical use. Differentiation progressed through a culture diversification recapitulating early embryonic development, whereby cells rapidly acquired a rostral embryo patterning signature before converging toward the RPE lineage. At intermediate steps, we identified and examined the potency of an NCAM1

Identifiants

pubmed: 35705015
pii: S2213-6711(22)00257-0
doi: 10.1016/j.stemcr.2022.05.005
pmc: PMC9214069
pii:
doi:

Substances chimiques

Retinal Pigments 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1458-1475

Subventions

Organisme : NCI NIH HHS
ID : P50 CA211015
Pays : United States

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Sandra Petrus-Reurer (S)

Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden.

Alex R Lederer (AR)

Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Laura Baqué-Vidal (L)

Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.

Iyadh Douagi (I)

Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.

Belinda Pannagel (B)

Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.

Irina Khven (I)

Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Monica Aronsson (M)

Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden.

Hammurabi Bartuma (H)

Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden.

Magdalena Wagner (M)

Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.

Andreas Wrona (A)

Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark.

Paschalis Efstathopoulos (P)

Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark.

Elham Jaberi (E)

Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark.

Hanni Willenbrock (H)

Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark.

Yutaka Shimizu (Y)

Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark.

J Carlos Villaescusa (JC)

Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark.

Helder André (H)

Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden.

Erik Sundstrӧm (E)

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 17177 Stockholm, Sweden.

Aparna Bhaduri (A)

Department of Neurology, University of California, San Francisco, CA, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA.

Arnold Kriegstein (A)

Department of Neurology, University of California, San Francisco, CA, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA.

Anders Kvanta (A)

Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden.

Gioele La Manno (G)

Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: gioele.lamanno@epfl.ch.

Fredrik Lanner (F)

Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden; Ming Wai Lau Center for Reparative Medicine, Stockholm node, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address: fredrik.lanner@ki.se.

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Classifications MeSH