Modelling ciliopathy phenotypes in human tissues derived from pluripotent stem cells with genetically ablated cilia.

ABSTRACT: The functions of cilia-antenna-like organelles associated with a spectrum of disease states-are poorly understood, particularly in human cells. Here we show that human pluripotent stem cells (hPSCs) edited via CRISPR to knock out the kinesin-2 subunits KIF3A or KIF3B can be used to model ciliopathy phenotypes and to reveal ciliary functions at the tissue scale. KIF3A^-/- and KIF3B^-/- hPSCs lacked cilia, yet remained robustly self-renewing and pluripotent. Tissues and organoids derived from these hPSCs displayed phenotypes that recapitulated defective neurogenesis and nephrogenesis, polycystic kidney disease (PKD) and other features of the ciliopathy spectrum. We also show that human cilia mediate a critical switch in hedgehog signalling during organoid differentiation,

SUBMITTER: Cruz NM 

PROVIDER: S-EPMC9228023 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature