Citrin-deficient Patient-derived Induced Pluripotent Stem Cells As a Pathological Liver Model for Congenital Urea Cycle Disorders

Overview

Journal Mol Genet Metab Rep

Specialty Endocrinology

Date 2024 Jun 14

PMID 38872960

Authors

Mai Okano

Masahiro Yasuda

Yui Shimomura

Yoshikazu Matsuoka

Yasumasa Shirouzu

Tatsuya Fujioka

Masatoshi Kyo

Shoji Tsuji

Kazunari Kaneko

Hirofumi Hitomi

Affiliations

Soon will be listed here.

Abstract

Citrin deficiency is a congenital secondary urea cycle disorder lacking useful disease models for effective treatment development. In this study, human induced pluripotent stem cells (iPSCs) were generated from two patients with citrin deficiency and differentiated into hepatocyte-like cells (HLCs). Citrin-deficient HLCs produced albumin and liver-specific markers but completely lacked citrin protein and expressed argininosuccinate synthase only weakly. In addition, ammonia concentrations in a medium cultured with citrin-deficient HLCs were higher than with control HLCs. Sodium pyruvate administration significantly reduced ammonia concentrations in the medium of citrin-deficient HLCs and slightly reduced ammonia in HLCs differentiated from control iPSCs, though this change was not significant. Our results suggest that sodium pyruvate may be an efficient treatment for patients with citrin deficiency. Citrin-deficient iPSCs are a pathological liver model for congenital urea cycle disorders to clarify pathogenesis and develop novel therapies.

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