{"id":"https://openalex.org/W4412867290","doi":"https://doi.org/10.1101/2025.08.02.668295","title":"Human retinal organoid single-cell atlas allows to reconstruct retinal development at high resolution and identify nature restricted transcriptional states in vitro","display_name":"Human retinal organoid single-cell atlas allows to reconstruct retinal development at high resolution and identify nature restricted transcriptional states in vitro","publication_year":2025,"publication_date":"2025-08-02","ids":{"openalex":"https://openalex.org/W4412867290","doi":"https://doi.org/10.1101/2025.08.02.668295"},"language":"en","primary_location":{"id":"doi:10.1101/2025.08.02.668295","doi":"https://doi.org/10.1101/2025.08.02.668295","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2025.08.02.668295","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.1101/2025.08.02.668295","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5113259901","display_name":"Emil Kriukov","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1287163989","display_name":"Massachusetts Eye and Ear Infirmary","ror":"https://ror.org/04g3dn724","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1287163989"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Emil Kriukov","raw_affiliation_strings":["Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","Department of Ophthalmology, Harvard Medical School, Boston, MA","Massachusetts Eye and Ear, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","institution_ids":["https://openalex.org/I1287163989","https://openalex.org/I136199984"]},{"raw_affiliation_string":"Department of Ophthalmology, Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Massachusetts Eye and Ear, Boston, MA","institution_ids":["https://openalex.org/I1287163989"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5114322874","display_name":"Everett Labrecque","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1287163989","display_name":"Massachusetts Eye and Ear Infirmary","ror":"https://ror.org/04g3dn724","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1287163989"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Everett Labrecque","raw_affiliation_strings":["Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","Department of Ophthalmology, Harvard Medical School, Boston, MA","Massachusetts Eye and Ear, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","institution_ids":["https://openalex.org/I1287163989","https://openalex.org/I136199984"]},{"raw_affiliation_string":"Department of Ophthalmology, Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Massachusetts Eye and Ear, Boston, MA","institution_ids":["https://openalex.org/I1287163989"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070855654","display_name":"Nasrin Refaian","orcid":"https://orcid.org/0000-0001-8345-5972","observed_orcids":["https://orcid.org/0000-0001-8345-5972"]},"institutions":[{"id":"https://openalex.org/I1287163989","display_name":"Massachusetts Eye and Ear Infirmary","ror":"https://ror.org/04g3dn724","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1287163989"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nasrin Refaian","raw_affiliation_strings":["Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","Department of Ophthalmology, Harvard Medical School, Boston, MA","Massachusetts Eye and Ear, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","institution_ids":["https://openalex.org/I1287163989","https://openalex.org/I136199984"]},{"raw_affiliation_string":"Department of Ophthalmology, Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Massachusetts Eye and Ear, Boston, MA","institution_ids":["https://openalex.org/I1287163989"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5083336047","display_name":"Petr Y. Baranov","orcid":"https://orcid.org/0000-0002-5526-7058","observed_orcids":["https://orcid.org/0000-0002-5526-7058"]},"institutions":[{"id":"https://openalex.org/I1287163989","display_name":"Massachusetts Eye and Ear Infirmary","ror":"https://ror.org/04g3dn724","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1287163989"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Petr Baranov","raw_affiliation_strings":["Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","Department of Ophthalmology, Harvard Medical School, Boston, MA","Massachusetts Eye and Ear, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Schepens Eye Research Institute of Mass Eye and Ear; Department of Ophthalmology, Harvard Medical School","institution_ids":["https://openalex.org/I1287163989","https://openalex.org/I136199984"]},{"raw_affiliation_string":"Department of Ophthalmology, Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Massachusetts Eye and Ear, Boston, MA","institution_ids":["https://openalex.org/I1287163989"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5083336047"],"corresponding_institution_ids":["https://openalex.org/I1287163989","https://openalex.org/I136199984"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10691","display_name":"Retinal Development and Disorders","score":0.7505000233650208,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10691","display_name":"Retinal Development and Disorders","score":0.7505000233650208,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11289","display_name":"Single-cell and spatial transcriptomics","score":0.2378000020980835,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10505","display_name":"Pluripotent Stem Cells Research","score":0.002899999963119626,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/retinal-organoids","display_name":"retinal organoids","score":0.9200000166893005},{"id":"https://openalex.org/keywords/retinal-development","display_name":"retinal development","score":0.902999997138977},{"id":"https://openalex.org/keywords/single-cell-transcriptomics","display_name":"single-cell transcriptomics","score":0.7760000228881836},{"id":"https://openalex.org/keywords/pluripotent-stem-cell-differentiation","display_name":"pluripotent stem cell differentiation","score":0.8610000014305115},{"id":"https://openalex.org/keywords/retinal-cell-types","display_name":"retinal cell types","score":0.800000011920929},{"id":"https://openalex.org/keywords/neuronal-maturation","display_name":"neuronal maturation","score":0.722000002861023},{"id":"https://openalex.org/keywords/developmental-plasticity","display_name":"developmental plasticity","score":0.7039999961853027},{"id":"https://openalex.org/keywords/chimeric-cells","display_name":"chimeric cells","score":0.7889999747276306},{"id":"https://openalex.org/keywords/blindness","display_name":"blindness","score":0.5099999904632568},{"id":"https://openalex.org/keywords/regenerative-medicine","display_name":"regenerative medicine","score":0.8349999785423279}],"concepts":[{"id":"https://openalex.org/C2780827179","wikidata":"https://www.wikidata.org/wiki/Q422001","display_name":"Retinal","level":2,"score":0.7630259990692139},{"id":"https://openalex.org/C31695470","wikidata":"https://www.wikidata.org/wiki/Q11293125","display_name":"Organoid","level":2,"score":0.7383353114128113},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.4783986806869507},{"id":"https://openalex.org/C2776673561","wikidata":"https://www.wikidata.org/wiki/Q655357","display_name":"Atlas (anatomy)","level":2,"score":0.46836957335472107},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.46636900305747986},{"id":"https://openalex.org/C3020199158","wikidata":"https://www.wikidata.org/wiki/Q210521","display_name":"High resolution","level":2,"score":0.45425179600715637},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.40469789505004883},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4041484594345093},{"id":"https://openalex.org/C31972630","wikidata":"https://www.wikidata.org/wiki/Q844240","display_name":"Computer vision","level":1,"score":0.3741625249385834},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.32683098316192627},{"id":"https://openalex.org/C105702510","wikidata":"https://www.wikidata.org/wiki/Q514","display_name":"Anatomy","level":1,"score":0.23118886351585388},{"id":"https://openalex.org/C205649164","wikidata":"https://www.wikidata.org/wiki/Q1071","display_name":"Geography","level":0,"score":0.2067621648311615},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.18640989065170288},{"id":"https://openalex.org/C62649853","wikidata":"https://www.wikidata.org/wiki/Q199687","display_name":"Remote sensing","level":1,"score":0.14638707041740417},{"id":"https://openalex.org/C59822182","wikidata":"https://www.wikidata.org/wiki/Q441","display_name":"Botany","level":1,"score":0.12709325551986694}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1101/2025.08.02.668295","doi":"https://doi.org/10.1101/2025.08.02.668295","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2025.08.02.668295","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1101/2025.08.02.668295","doi":"https://doi.org/10.1101/2025.08.02.668295","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2025.08.02.668295","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G5732853978","display_name":null,"funder_award_id":"GFF00","funder_id":"https://openalex.org/F4320316728","funder_display_name":"Gilbert Family Foundation"}],"funders":[{"id":"https://openalex.org/F4320316728","display_name":"Gilbert Family Foundation","ror":"https://ror.org/01kf4yp82"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":49,"referenced_works":["https://openalex.org/W1486226554","https://openalex.org/W1995545448","https://openalex.org/W2046681118","https://openalex.org/W2073947789","https://openalex.org/W2074314696","https://openalex.org/W2076900594","https://openalex.org/W2084637683","https://openalex.org/W2159555560","https://openalex.org/W2169353679","https://openalex.org/W2800392236","https://openalex.org/W2897249806","https://openalex.org/W2911551350","https://openalex.org/W2949177718","https://openalex.org/W2967177832","https://openalex.org/W3005472012","https://openalex.org/W3019589546","https://openalex.org/W3021129313","https://openalex.org/W3088521497","https://openalex.org/W3101477379","https://openalex.org/W3120365639","https://openalex.org/W3123185162","https://openalex.org/W3126216907","https://openalex.org/W3164692211","https://openalex.org/W3165128404","https://openalex.org/W3196650609","https://openalex.org/W3207466490","https://openalex.org/W4210604271","https://openalex.org/W4220953126","https://openalex.org/W4225598893","https://openalex.org/W4310087933","https://openalex.org/W4376133488","https://openalex.org/W4378212544","https://openalex.org/W4385697698","https://openalex.org/W4386149838","https://openalex.org/W4387451658","https://openalex.org/W4388406906","https://openalex.org/W4392382547","https://openalex.org/W4394717503","https://openalex.org/W4395031805","https://openalex.org/W4399781483","https://openalex.org/W4400578734","https://openalex.org/W4402314647","https://openalex.org/W4404566892","https://openalex.org/W4407757607","https://openalex.org/W4408866491","https://openalex.org/W4411235158","https://openalex.org/W4411900437","https://openalex.org/W4413947724","https://openalex.org/W4415648807"],"related_works":["https://openalex.org/W7221441917","https://openalex.org/W4315489784","https://openalex.org/W3118034245","https://openalex.org/W4283014723","https://openalex.org/W7027445384","https://openalex.org/W3087102910","https://openalex.org/W4379209041","https://openalex.org/W7160819820","https://openalex.org/W4401688871","https://openalex.org/W6906579425"],"abstract_inverted_index":{"Abstract":[0],"The":[1],"vertebrate":[2],"retina":[3,170],"is":[4],"a":[5,50,117,145,237],"highly":[6],"specialized":[7],"neural":[8],"structure":[9],"crucial":[10,238],"for":[11,99,148,240],"the":[12,34,74,85,110,167],"initial":[13],"capture":[14],"and":[15,28,56,69,81,104,139,156,181,193,213,247],"processing":[16],"of":[17,31,36,54,60,83,87,201],"visual":[18],"information.":[19],"Perturbations":[20],"in":[21,179,182,190,231,251],"retinal":[22,39,45,61,67,123,153,184,202,222,242],"development":[23,68,86,125],"contribute":[24],"significantly":[25],"to":[26,129,220],"congenital":[27],"acquired":[29],"forms":[30],"blindness,":[32],"underscoring":[33],"necessity":[35],"elucidating":[37],"human":[38,168],"ontogeny.":[40],"Human":[41,111],"pluripotent":[42],"stem":[43],"cell-derived":[44],"organoids":[46],"have":[47],"emerged":[48],"as":[49,210,236],"powerful":[51],"model":[52],"capable":[53],"self-organizing":[55],"recapitulating":[57],"key":[58],"aspects":[59],"morphogenesis,":[62],"offering":[63],"valuable":[64],"insights":[65],"into":[66],"disease.":[70],"Despite":[71],"their":[72,101],"utility,":[73],"extensive":[75],"cellular":[76,158],"heterogeneity,":[77],"dynamic":[78],"state":[79],"transitions,":[80],"existence":[82],"unique,":[84],"this":[88],"system":[89],"has":[90],"not":[91,218],"yet":[92],"been":[93],"fully":[94],"resolved,":[95],"posing":[96],"significant":[97],"challenges":[98],"interpreting":[100],"developmental":[102,194,203,229],"fidelity":[103],"therapeutic":[105],"applicability.":[106],"Here,":[107],"we":[108,173],"present":[109],"Retinal":[112],"Organoid":[113],"Cell":[114],"Atlas":[115],"(HROCA),":[116],"comprehensive":[118],"single-cell":[119,161],"transcriptomic":[120],"reference":[121],"spanning":[122],"organoid":[124,149,245],"from":[126,134],"Day":[127,130],"10":[128],"365,":[131],"integrating":[132],"data":[133],"15":[135],"studies,":[136],"71":[137],"batches,":[138],"encompassing":[140],"458,309":[141],"cells.":[142],"HROCA":[143,165,197],"provides":[144],"detailed":[146],"benchmark":[147],"differentiation,":[150],"identifying":[151],"known":[152],"cell":[154,207,223],"classes":[155],"novel":[157],"states":[159],"at":[160],"resolution.":[162],"By":[163],"associating":[164],"with":[166],"fetal":[169],"atlas":[171,234],"(HFR),":[172],"offer":[174],"an":[175],"in-depth":[176],"comparison":[177],"between":[178],"vitro":[180],"vivo":[183],"development,":[185,243],"revealing":[186],"protocol-specific":[187],"differences,":[188],"limitations":[189],"neuronal":[191],"maturation,":[192],"timing":[195],"discrepancies.":[196],"expands":[198],"our":[199],"understanding":[200,241],"plasticity,":[204],"highlighting":[205],"unique":[206],"populations":[208],"such":[209],"chimeric,":[211],"non-canonical,":[212],"apatride":[214],"cells,":[215],"which":[216],"do":[217],"conform":[219],"classical":[221],"types":[224],"but":[225],"exist":[226],"consistently":[227],"across":[228],"timelines":[230],"vitro.":[232],"This":[233],"serves":[235],"resource":[239],"evaluating":[244],"models,":[246],"guiding":[248],"future":[249],"improvements":[250],"regenerative":[252],"medicine":[253],"strategies.":[254]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-10-17T09:40:24.721904","created_date":"2025-10-10T00:00:00"}