Generation and Characterization of Novel iPSC Lines from a Portuguese Family Bearing Heterozygous and Homozygous GRN Mutations

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Oliveira, AR (Author) Other; Martins, S (Author) Other; Cammarata, G (Author) Other; Martins, M (Author) Other; Cardoso, AM (Author) Other; Almeida, MR (Author) Other; Macario, MD (Author) Other; Santana, I (Author) Other; Peca, J (Author) Other; Cardoso, AL (Author) Other

Journal

Title: Biomedicines

Vol. 10

Final page: 1905

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus

Other information

Authenticus ID: P-00X-54F

DOI: 10.3390/biomedicines10081905

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17