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Tay Sachs disease variant B1: iPSC and NGS as the basis for a cellular model

2022-09Conference object Open access
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dc.contributor.authorRibeiro, Diogo
dc.contributor.authorDuarte, Ana J.
dc.contributor.authorMoreira, Luciana
dc.contributor.authorSantos, Renato
dc.contributor.authorEncarnaçao, Marisa
dc.contributor.authorSilva, Lisbeth
dc.contributor.authorCoutinho, M. Francisca
dc.contributor.authorAlves, Sandra
dc.contributor.authorAmaral, Olga
dc.date.accessioned2022-11-02T14:08:25Z
dc.date.available2022-11-02T14:08:25Z
dc.date.issued2022-09
dc.description.abstractTay Sachs disease variant B1 (TSD B1; OMIM 272800) is a neurodegenerative lysosomal storage disease (LSD) which, although rare, is the most frequent form of TSD in Portugal. The mutation p.R178H (c.533G>A; rs28941770), associated with TSD B1, leads to a mutant HexA protein with altered kinetics and reduced residual activity. The availability of disease-relevant cell types derived from induced pluripotent stem cells (iPSCs) provides a model for studying the pathogenic mechanisms and, eventually, test therapeutic approaches for TSD B1 patients. The main objectives of this project is, by using iPSCs, to generate a neuronal TSD B1 specific cellular model and to implement the genetic profiling by Next Generation Sequencing (NGS) to examine potential changes in the manipulated cells. In the present work, the iPSC reprogramming and differentiation into neural progenitor cells (NPCs) is presented, as well as the NGS results from the donor cells. As a first step, iPSCs from a control fibroblast cell line and from TSD B1 fibroblasts were obtained by using a non-integrative approach with episomal vectors, the control was further differentiated into NPCs. When generating iPSCs it is important to have multiple characterisation steps. The iPSCs have to mimic the donor background at genetic and protein levels. Furthermore, iPSCs or iPSC-derived lines need to be free of the reprogramming and differentiation markers while presenting specific cell-type markers. The frailty of these cells and adverse conditions (first lockdowns and later accidental deprivation of liquid nitrogen) led to the interruption of the iPSC work. In the meantime, we did a lysosomal-related gene profiling of the DNA from the original cell lines. By using an in-house customized NGS panel, we obtained results of the cells in a “naïve” state to later compare with TSD B1 iPSCs and NPCs obtained from control iPSCs. The results presented consist of the preliminary work to obtain a cell model of TS-B1.pt_PT
dc.description.sponsorshipAlthough project FCT, PTDC/BIM-MEC/4762/2014 ended in 2020 part of the personal grants and consumables related to this work were supported by this project. This work is part of the PhD thesis project of D. Ribeiro at ICBAS (2018DGH1576).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/8295
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectTay Sachs B1 variantpt_PT
dc.subjectLysossomal Disorderpt_PT
dc.subjectCell Modelspt_PT
dc.subjectHuman Geneticspt_PT
dc.subjectiPSCpt_PT
dc.subjectNGSpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleTay Sachs disease variant B1: iPSC and NGS as the basis for a cellular modelpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIM-MEC%2F4762%2F2014/PT
oaire.citation.conferencePlaceLancaster, UKpt_PT
oaire.citation.title24th ESGLD- European Study Group on Lysosomal Disorders Workshop, 7-11 set 2022pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameAmaral
person.givenNameOlga
person.identifier.ciencia-id6F1F-54A3-BBB9
person.identifier.orcid0000-0002-3478-2122
person.identifier.scopus-author-id7004054964
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isAuthorOfPublication8c7fb04a-80c0-4dd7-b3c5-682f6d25662b
relation.isAuthorOfPublication.latestForDiscovery8c7fb04a-80c0-4dd7-b3c5-682f6d25662b
relation.isProjectOfPublication9452b84c-9691-47bb-82ba-75ed40cdfa04
relation.isProjectOfPublication.latestForDiscovery9452b84c-9691-47bb-82ba-75ed40cdfa04

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