Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

BBS Proteins Affect Ciliogenesis and Are Essential for Hedgehog Signaling, but Not for Formation of iPSC-Derived RPE-65 Expressing RPE-Like Cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Regional Differences in Neuroinflammation-Associated Gene Expression in the Brain of Sporadic Creutzfeldt-Jakob Disease Patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

    Publikation: Bidrag til tidsskriftReviewpeer review

  1. Deciphering the premature mortality in PIGA-CDG - An untold story

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Crosstalk of Hedgehog and mTORC1 Pathways

    Publikation: Bidrag til tidsskriftReviewpeer review

  3. Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A)

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal dystrophy, renal cysts, obesity and polydactyly. BBS genes have been implicated in ciliogenesis, hedgehog signaling and retinal pigment epithelium maturation. BBS1 and BBS5 are members of the BBSome, implicated in cilia transport of proteins, and BBS10 is a member of the chaperonin-complex, mediating BBSome assembly. In this study, involvement of BBS1, BBS5 and BBS10 in ciliogenesis and hedgehog signaling were investigated in BBS-defective patient fibroblasts as well as in RPE-hTERT cells following siRNA-mediated knockdown of the BBS genes. Furthermore, the ability of BBS1-defective induced pluripotent stem-cells (iPSCs) to differentiate into RPE cells was assessed. We report that cells lacking functional BBS5 or BBS10 have a reduced number of primary cilia, whereas cells lacking functional BBS1 display shorter primary cilia compared to wild-type cells. Hedgehog signaling was substantially impaired and Smoothened, a component of hedgehog signaling, was trapped inside the cilia of the BBS-defective cells, even in the absence of Smoothened agonist. Preliminary results demonstrated the ability of BBS1-defective iPSC to differentiate into RPE-65 expressing RPE-like cells. The BBS1-/--defective RPE-like cells were less pigmented, compared to RPE-like cells differentiated from control iPSCs, indicating an impact of BBS1 on RPE maturation.

OriginalsprogEngelsk
TidsskriftInternational Journal of Molecular Sciences
Vol/bind22
Udgave nummer3
Sider (fra-til)1345
ISSN1661-6596
DOI
StatusUdgivet - 29 jan. 2021

ID: 62413132