Generation and characterization of a human iPSC line (UAMi005-A) from a patient with nonketotic hyperglycinemia due to mutations in the GLDC gene

Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient

“…To determine the potential of iPSCs to mimic GLDC deficiency, we examined the expression of GLDC , AMT , and GCSH in these cells. We evaluated both control and GLDC27-FiPS4F-1 iPSCs [ 15 ], obtained by reprogramming dermal fibroblasts using the CytoTune™ iPS Reprogramming kit delivering the four human reprogramming factors OCT3/4 , SOX2 , c-MYC , and KLF4 [ 17 ]. These cell lines were previously characterized for pluripotency, normal karyotype, and line identity through short tandem repeat analysis.…”

“…The primary aim of this study was to establish a valid human model of GLDC deficiency to serve as a basis for testing potential therapeutic strategies in nonketotic hyperglycinemia (NKH). We generated a human iPSC line that exhibited biochemical characteristics of GLDC deficiency while maintaining pluripotency, the capability to differentiate into three germ layers, and genomic stability [ 15 ]. The GLDC27-FiPS4F-1 line showed a noteworthy decrease in the amounts of GCSP protein and the assembled GCS complex.…”

“…One healthy control iPSC line (registered as FiPS Ctrl2-SV4F-1), matched for age, sex, ethnicity, and reprograming method with the GLDC27-FiPS4F-1 line used in this study, was obtained from the Banco Nacional de Líneas Celulares of the Instituto de Salud Carlos III. The GLDC27-FiPS4F-1 line was reprogrammed at our laboratory [ 15 ] from NKH patient-derived fibroblasts who suffered a severe clinical course and bore the biallelic changes c.1742C > G (p.Pro581Arg) and c.2368C > T (p.Arg790Trp) in the GLDC gene that led to a significant decrease in protein levels and exchange activity in vitro, as previously described [ 16 ]. These were then registered in the Banco Nacional de Líneas Celulares of the Instituto de Salud Carlos III as GLDC27-FiPS4F-1.…”

“…Our analysis focused on astrocytes, which comprise most of the cell population in the human brain and play a key role in serine–glycine–one-carbon metabolism. We utilized a human induced pluripotent stem cell (iPSC) model [ 15 ] derived from fibroblasts of a patient with severe NKH with hypomorphic GLDC mutations [ 16 ] to investigate the effects of GLDC deficiency on cell metabolism, bioenergetics, growth, and cell cycle, from pluripotent iPSCs to differentiated neural cells.…”

Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocytes Model Derived From a Nonketotic Hyperglycinemia Patient

“…One healthy control iPSC line (registered as FiPS Ctrl2-SV4F-1), matched for age, sex, ethnicity, and reprograming method with the GLDC27-FiPS4F-1 line used in this study, was obtained from the Banco Nacional de Líneas Celulares of the Instituto de Salud Carlos III. The GLDC27-FiPS4F-1 line was reprogrammed at our laboratory [15] from NKH patientderived fibroblasts who suffered a severe clinical course and bore the biallelic changes c.1742C > G (p.Pro581Arg) and c.2368C > T (p.Arg790Trp) in the GLDC gene that led to a significant decrease in protein levels and exchange activity in vitro, as previously described [16]. These were then registered in the Banco Nacional de Líneas Celulares of the Instituto de Salud Carlos III as GLDC27-FiPS4F-1.…”