Downregulation of PMP22 ameliorates myelin defects in iPSC-derived human organoid cultures of CMT1A.

ABSTRACT: Charcot-Marie-Tooth disease is the most common inherited disorder of the PNS. CMT1A accounts for 40-50% of all cases and is caused by a duplication of the PMP22 gene on chromosome 17, leading to dysmyelination in the PNS. Patient-derived models to study such myelination defects are lacking as the in vitro generation of human myelinating Schwann cells has proved to be particularly challenging. Here, we present an induced pluripotent stem cell-derived organoid culture, containing various cell types of the PNS, including myelinating human Schwann cells, which mimics the human PNS. Single-cell analysis confirmed the PNS-like cellular composition and provides insight into the developmental trajectory. We used this organoid model to study disease signatures of CMT1A, revealing early ultrastructu

SUBMITTER: Van Lent J 

PROVIDER: S-EPMC10316758 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature