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Transcriptome profiling of human pluripotent stem cell‐derived cerebellar organoids reveals faster commitment under dynamic conditions

2021Journal article Restricted access
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dc.contributor.authorSilva, Teresa P.
dc.contributor.authorSousa-Luis, Rui
dc.contributor.authorFernandes, Tiago G.
dc.contributor.authorBekman, Evguenia
dc.contributor.authorRodrigues, Carlos A.V.
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorMoreira, Leonilde M.
dc.contributor.authorHashimura, Yas
dc.contributor.authorJung, Sunghoon
dc.contributor.authorLee, Brian
dc.contributor.authorCarmo-Fonseca, Maria
dc.contributor.authorCabral, Joaquim M.S.
dc.date.accessioned2021-05-21T14:33:54Z
dc.date.available2021-05-21T14:33:54Z
dc.date.issued2021
dc.description© 2021 Wiley Periodicals LLCpt_PT
dc.description.abstractHuman-induced pluripotent stem cells (iPSCs) have great potential for disease modeling. However, generating iPSC-derived models to study brain diseases remains a challenge. In particular, the ability to recapitulate cerebellar development in vitro is still limited. We presented a reproducible and scalable production of cerebellar organoids by using the novel single-use Vertical-Wheel bioreactors, in which functional cerebellar neurons were obtained. Here, we evaluate the global gene expression profiles by RNA sequencing (RNA-seq) across cerebellar differentiation, demonstrating a faster cerebellar commitment in this novel dynamic differentiation protocol. Furthermore, transcriptomic profiles suggest a significant enrichment of extracellular matrix (ECM) in dynamic-derived cerebellar organoids, which can better mimic the neural microenvironment and support a consistent neuronal network. Thus, an efficient generation of organoids with cerebellar identity was achieved for the first time in a continuous process using a dynamic system without the need of organoids encapsulation in ECM-based hydrogels, allowing the possibility of large-scale production and application in high-throughput processes. The presence of factors that favors angiogenesis onset was also detected in dynamic conditions, which can enhance functional maturation of cerebellar organoids. We anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests, and studying pathological pathways involved in cerebellar degeneration.pt_PT
dc.description.sponsorshipThis study was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal (UIDB/04565/2020 through Programa Operacional Regional de Lisboa 2020, Project no. 007317, PD/BD/105773/2014 to Teresa P. Silva and SFRH/BD/147906/2019 to Rui Sousa-Luís), projects co-funded by FEDER (POR Lisboa 2020—Programa Operacional Regional de Lisboa PORTUGAL 2020) and FCT through Grant PAC-PRECISE LISBOA-01-0145-FEDER-016394 and CEREBEX Generation of Cerebellar Organoids for Ataxia Research Grant LISBOA-01-0145-FEDER-029298.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiotechnol Bioeng. 2021 Apr 19pt_PT
dc.identifier.doi10.1002/bit.27797pt_PT
dc.identifier.eissn1097-0290
dc.identifier.issn0006-3592
dc.identifier.urihttp://hdl.handle.net/10451/48084
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relationLISBOA-01-0145-FEDER-016394pt_PT
dc.relationInstitute for Bioengineering and Biosciences
dc.relationA DEFINIR
dc.relationTuning of protein coding gene expression by promoter-proximal convergent antisense transcription
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/10970290pt_PT
dc.subjectCerebellumpt_PT
dc.subjectDynamic conditionspt_PT
dc.subjectHuman pluripotent stem cellspt_PT
dc.subjectLarge‐scale productionpt_PT
dc.subjectOrganoidspt_PT
dc.titleTranscriptome profiling of human pluripotent stem cell‐derived cerebellar organoids reveals faster commitment under dynamic conditionspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleInstitute for Bioengineering and Biosciences
oaire.awardTitleA DEFINIR
oaire.awardTitleTuning of protein coding gene expression by promoter-proximal convergent antisense transcription
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04565%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F105773%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F147906%2F2019/PT
oaire.citation.titleBiotechnology and Bioengineeringpt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
person.familyNameSilva
person.familyNameSousa-Luís
person.familyNameFernandes
person.familyNameBekman
person.familyNameVitorino Rodrigues
person.familyNameHenriques Vaz
person.familyNameCarmo-Fonseca
person.familyNameCabral
person.givenNameTeresa P.
person.givenNameRui
person.givenNameTiago
person.givenNameEvguenia
person.givenNameCarlos André
person.givenNameSandra Cristina
person.givenNameMaria
person.givenNameJoaquim M.S.
person.identifier833090
person.identifier693442
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person.identifier.ciencia-idB31F-0435-0753
person.identifier.ciencia-idAB13-9ED3-C821
person.identifier.orcid0000-0002-5039-703X
person.identifier.orcid0000-0002-2589-144X
person.identifier.orcid0000-0002-4651-2832
person.identifier.orcid0000-0002-3963-1358
person.identifier.orcid0000-0001-9645-1591
person.identifier.orcid0000-0003-4258-9397
person.identifier.orcid0000-0002-3402-7143
person.identifier.orcid0000-0002-2405-5845
person.identifier.ridC-3865-2009
person.identifier.ridO-9840-2017
person.identifier.ridG-2052-2010
person.identifier.scopus-author-id22934439300
person.identifier.scopus-author-id6602470751
person.identifier.scopus-author-id7007128195
person.identifier.scopus-author-id7201350203
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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