Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell level
Summary: Molecular information on the early stages of human retinal development remains scarce due to limitations in obtaining early human eye samples. Pluripotent stem cell-derived retinal organoids (ROs) provide an unprecedented opportunity for studying early retinogenesis. Using a combination of...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224006187 |
| _version_ | 1827316919211917312 |
|---|---|
| author | Birthe Dorgau Joseph Collin Agata Rozanska Veronika Boczonadi Marina Moya-Molina Adrienne Unsworth Rafiqul Hussain Jonathan Coxhead Tamil Dhanaseelan Lyle Armstrong Rachel Queen Majlinda Lako |
| author_facet | Birthe Dorgau Joseph Collin Agata Rozanska Veronika Boczonadi Marina Moya-Molina Adrienne Unsworth Rafiqul Hussain Jonathan Coxhead Tamil Dhanaseelan Lyle Armstrong Rachel Queen Majlinda Lako |
| author_sort | Birthe Dorgau |
| collection | DOAJ |
| description | Summary: Molecular information on the early stages of human retinal development remains scarce due to limitations in obtaining early human eye samples. Pluripotent stem cell-derived retinal organoids (ROs) provide an unprecedented opportunity for studying early retinogenesis. Using a combination of single cell RNA-seq and spatial transcriptomics we present for the first-time a single cell spatiotemporal transcriptome of RO development. Our data demonstrate that ROs recapitulate key events of retinogenesis including optic vesicle/cup formation, presence of a putative ciliary margin zone, emergence of retinal progenitor cells and their orderly differentiation to retinal neurons. Combining the scRNA- with scATAC-seq data, we were able to reveal cell-type specific transcription factor binding motifs on accessible chromatin at each stage of organoid development, and to show that chromatin accessibility is highly correlated to the developing human retina, but with some differences in the temporal emergence and abundance of some of the retinal neurons. |
| first_indexed | 2024-04-24T23:23:51Z |
| format | Article |
| id | doaj.art-75b0f3cd2f454035b6357992656fba5c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T23:23:51Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-75b0f3cd2f454035b6357992656fba5c2024-03-16T05:08:58ZengElsevieriScience2589-00422024-04-01274109397Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell levelBirthe Dorgau0Joseph Collin1Agata Rozanska2Veronika Boczonadi3Marina Moya-Molina4Adrienne Unsworth5Rafiqul Hussain6Jonathan Coxhead7Tamil Dhanaseelan8Lyle Armstrong9Rachel Queen10Majlinda Lako11Biosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK; Newcells Biotech, Newcastle upon Tyne NE4 5BX, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UKBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK; Corresponding authorBiosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK; Corresponding authorSummary: Molecular information on the early stages of human retinal development remains scarce due to limitations in obtaining early human eye samples. Pluripotent stem cell-derived retinal organoids (ROs) provide an unprecedented opportunity for studying early retinogenesis. Using a combination of single cell RNA-seq and spatial transcriptomics we present for the first-time a single cell spatiotemporal transcriptome of RO development. Our data demonstrate that ROs recapitulate key events of retinogenesis including optic vesicle/cup formation, presence of a putative ciliary margin zone, emergence of retinal progenitor cells and their orderly differentiation to retinal neurons. Combining the scRNA- with scATAC-seq data, we were able to reveal cell-type specific transcription factor binding motifs on accessible chromatin at each stage of organoid development, and to show that chromatin accessibility is highly correlated to the developing human retina, but with some differences in the temporal emergence and abundance of some of the retinal neurons.http://www.sciencedirect.com/science/article/pii/S2589004224006187GeneticsMolecular biologyNeuroscienceCell biologyOmics |
| spellingShingle | Birthe Dorgau Joseph Collin Agata Rozanska Veronika Boczonadi Marina Moya-Molina Adrienne Unsworth Rafiqul Hussain Jonathan Coxhead Tamil Dhanaseelan Lyle Armstrong Rachel Queen Majlinda Lako Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell level iScience Genetics Molecular biology Neuroscience Cell biology Omics |
| title | Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell level |
| title_full | Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell level |
| title_fullStr | Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell level |
| title_full_unstemmed | Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell level |
| title_short | Deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single-cell level |
| title_sort | deciphering the spatiotemporal transcriptional and chromatin accessibility of human retinal organoid development at the single cell level |
| topic | Genetics Molecular biology Neuroscience Cell biology Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224006187 |
| work_keys_str_mv | AT birthedorgau decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT josephcollin decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT agatarozanska decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT veronikaboczonadi decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT marinamoyamolina decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT adrienneunsworth decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT rafiqulhussain decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT jonathancoxhead decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT tamildhanaseelan decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT lylearmstrong decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT rachelqueen decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel AT majlindalako decipheringthespatiotemporaltranscriptionalandchromatinaccessibilityofhumanretinalorganoiddevelopmentatthesinglecelllevel |