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In Portugal, GRN mutations account for around half of all FTLD cases with known genetic origin. Here, we describe the generation and characterization of three human-induced pluripotent stem cell (hiPSC) lines from a Portuguese family harboring heterozygous and homozygous GRN mutation. hiPSCs were reprogrammed from human dermal fibroblasts by episomal nucleofection of the Yamanaka factors. The new generated lines were positive for pluripotency markers, could be further differentiated to cells expressing all trilineage markers, and presented a normal karyotype. They were also capable of differentiating into 3D brain organoids and presented a significant decrease in progranulin protein levels. Hence, these cell lines constitute suitable new tools to elucidate the pathophysiological mechanisms associated with the GRN mutations in the context of FTLD.<\/jats:p>","DOI":"10.3390\/biomedicines10081905","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T21:03:50Z","timestamp":1659906230000},"page":"1905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Generation and Characterization of Novel iPSC Lines from a Portuguese Family Bearing Heterozygous and Homozygous GRN Mutations"],"prefix":"10.3390","volume":"10","author":[{"given":"Ana Rafaela","family":"Oliveira","sequence":"first","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"MIT-Portugal Ph.D. Program, NOVA School of Science and Technology, New University of Lisbon, 2829-516 Caparica, Portugal"}]},{"given":"Solange","family":"Martins","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Giuseppe","family":"Cammarata","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Mariana","family":"Martins","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1629-4782","authenticated-orcid":false,"given":"Ana Maria","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal"}]},{"given":"Maria Ros\u00e1rio","family":"Almeida","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Maria","family":"do Carmo Mac\u00e1rio","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Neurology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Isabel","family":"Santana","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Neurology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-2129","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Pe\u00e7a","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3000-456 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-4561","authenticated-orcid":false,"given":"Ana Lu\u00edsa","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/nature05016","article-title":"Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17","volume":"442","author":"Baker","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/nature05017","article-title":"Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21","volume":"442","author":"Cruts","year":"2006","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s00415-019-09363-4","article-title":"An update on genetic frontotemporal 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