Telomere Dysfunction Activates p53 and Represses HNF4α Expression Leading to Impaired Human Hepatocyte Development and Function
Abstract
Telomere attrition is a major risk factor for end‐stage liver disease. Due to a lack of adequate models and intrinsic difficulties in studying telomerase in physiologically relevant cells, the molecular mechanisms responsible for liver disease in patients with telomere syndromes remain elusive. To circumvent that, we used genome editing to generate isogenic human embryonic stem cells (hESCs) harboring clinically relevant mutations in telomerase and subjected them to an in vitro, stage‐specific hepatocyte differentiation protocol that resembles hepatocyte development in vivo.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 26, 2020
- Source ID
- 10.1002/hep.31414
Entities
People
- Alexandre Teixeira Vessoni
- Evandro Luis Niero
- Ho‐chang Jeong
- Kirsten Ann Brenner
- Luis Francisco Zirnberger Batista
- Michael Munroe
- Wilson Chun Fok
Organizations
- Washington University in St. Louis