Generation and characterization of novel iPSC Lines from a portuguese family bearing heterozygous and homozygous GRN mutations

Ana Rafaela Oliveira, Solange Martins, Giuseppe Cammarata, Mariana Martins, Ana Maria Cardoso, Maria Rosário Almeida, Maria do Carmo Macário, Isabel Santana, João Peça, Ana Luísa Cardoso*

*Autor correspondente para este trabalho

Resultado de pesquisarevisão de pares

1 Citação (Scopus)

Resumo

Mutations in granulin (GRN) have been associated with neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). 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.

Idioma originalEnglish
Número do artigo1905
Número de páginas17
RevistaBiomedicines
Volume10
Número de emissão8
DOIs
Estado da publicaçãoPublicado - ago. 2022
Publicado externamenteSim

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