{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Woo DH"],"funding":["NIA NIH HHS","NIDDK NIH HHS"],"pagination":["397-405"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7900823"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(3)"],"pubmed_abstract":["Patients with dyskeratosis congenita (DC) suffer from stem cell failure in highly proliferative tissues, including the intestinal epithelium. Few therapeutic options exist for this disorder, and patients are treated primarily with bone marrow transplantation to restore hematopoietic function. Here, we generate isogenic DC patient and disease allele-corrected intestinal tissue using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene correction in induced pluripotent stem cells and directed differentiation. We show that DC tissue has suboptimal Wnt pathway activity causing intestinal stem cell failure and that enhanced expression of the telomere-capping protein TRF2, a Wnt target gene, can alleviate DC phenotypes. Treatment with the clinically relevant Wnt "],"journal":["Cell stem cell"],"pubmed_title":["Enhancing a Wnt-Telomere Feedback Loop Restores Intestinal Stem Cell Function in a Human Organotypic Model of Dyskeratosis Congenita."],"pmcid":["PMC7900823"],"funding_grant_id":["R21 AG054209","P30 DK050306","P01 AG031862"],"pubmed_authors":["Hoge C","Chen Q","Leu NA","Lengner CJ","Woo DH","Yang TL","Glineburg MR","Johnson FB"],"additional_accession":[]},"is_claimable":false,"name":"Enhancing a Wnt-Telomere Feedback Loop Restores Intestinal Stem Cell Function in a Human Organotypic Model of Dyskeratosis Congenita.","description":"Patients with dyskeratosis congenita (DC) suffer from stem cell failure in highly proliferative tissues, including the intestinal epithelium. Few therapeutic options exist for this disorder, and patients are treated primarily with bone marrow transplantation to restore hematopoietic function. Here, we generate isogenic DC patient and disease allele-corrected intestinal tissue using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene correction in induced pluripotent stem cells and directed differentiation. We show that DC tissue has suboptimal Wnt pathway activity causing intestinal stem cell failure and that enhanced expression of the telomere-capping protein TRF2, a Wnt target gene, can alleviate DC phenotypes. Treatment with the clinically relevant Wnt ","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Sep","modification":"2026-05-07T19:15:17.397Z","creation":"2021-02-26T08:19:05Z"},"accession":"S-EPMC7900823","cross_references":{"pubmed":["27545506"],"doi":["10.1016/j.stem.2016.05.024"]}}