HCA Data Explorer

Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution

Updated January 26, 2024

Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable "developed" state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.

Guglielmo RomaNovartis Institutes for Biomedical Research, 4056 Basel, Switzerland.guglielmo.roma@novartis.com
Florian NigschNovartis Institutes for Biomedical Research, 4056 Basel, Switzerland. florian.nigsch@novartis.com
Botond RoskaInstitute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Department of Ophthalmology, University of Basel, 4031 Basel, Switzerland. botond.roska@iob.ch
Cameron S Cowan1
Magdalena Renner2
Martina De Gennaro3
Brigitte Gross-Scherf1
David Goldblum4
Yanyan Hou3
Martin Munz1
Tiago M Rodrigues3
Jacek Krol1
Tamas Szikra1
Rachel Cuttat5
Annick Waldt5
Panagiotis Papasaikas6
Roland Diggelmann7
Claudia P Patino-Alvarez1
Patricia Galliker3
Stefan E Spirig3
Dinko Pavlinic3
Nadine Gerber-Hollbach4
Sven Schuierer5
Aldin Srdanovic8
Marton Balogh3
Riccardo Panero3
Akos Kusnyerik9
Arnold Szabo10
Michael B Stadler6
Selim Orgül4
Simone Picelli3
Pascal W Hasler4
Andreas Hierlemann7
Hendrik P N Scholl11
Guglielmo Roma5
Florian Nigsch12
Botond Roska13
1Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
2Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland.
3Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland.
4Department of Ophthalmology, University of Basel, 4031 Basel, Switzerland.
5Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland.
6Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.
7Bio Engineering Laboratory, Department of Biosystems Science and Engineering of ETH Zurich, 4058 Basel, Switzerland.
8Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
9Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Department of Ophthalmology, Semmelweis University, 1085 Budapest, Hungary.
10Department of Anatomy, Histology and Embryology, Semmelweis University, 1085 Budapest, Hungary.
11Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Department of Ophthalmology, University of Basel, 4031 Basel, Switzerland; Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD 21287, USA.
12Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland.
13Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Department of Ophthalmology, University of Basel, 4031 Basel, Switzerland.
Wei Kheng Teh

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/1dddae6e-3753-48af-b20e-fa22abad125d
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Analysis Portals

CZ CELLxGENECZ CELLxGENE
UCSC Cell BrowserUCSC Cell Browser

Project Label

HumanRetinaOrganoids

Species

Homo sapiens

Sample Type

2 sample types

Anatomical Entity

2 anatomical entities

Organ Part

2 organ parts

Selected Cell Types

2 cell types

Model Organ

eye

Disease Status (Specimen)

normal

Disease Status (Donor)

Unspecified

Development Stage

2 development stages

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

processedmatrixgeneration, rawmatrixgeneration

File Format

3 file formats

Cell Count Estimate

285.4k

Donor Count

6
h5ad3 file(s)rds36 file(s)xlsx1 file(s)