Young-Jun Choi, Melissa S Kim, Joshua H Rhoades, Nicolette M Johnson, Corbett T Berry, Sarah Root, Qijun Chen, Yuhua Tian, Rafael J Fernandez, Zvi Cramer, Stephanie Adams-Tzivelekidis, Ning Li, F Brad Johnson, Christopher J Lengner
BACKGROUND & AIMS: Dyskeratosis congenita (DC) is a telomere maintenance disorder caused primarily by mutations in the DKC1 gene. Patients with DC and related telomeropathies resulting from premature telomere dysfunction suffer from multi-organ failure. In the liver, DC patients present with nodular hyperplasia, steatosis, inflammation, and cirrhosis. However, the mechanism responsible for telomere dysfunction-induced liver disease remains unclear. METHODS: We used isogenic human induced pluripotent stem (iPS) cells harboring a causal DC mutation in DKC1, or a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-corrected control allele to model DC liver pathologies...
June 9, 2023: Cellular and Molecular Gastroenterology and Hepatology