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Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells

  1. Author:
    May-Simera, Helen Louise
    Wan, Qin
    Jha, Balendu Shekhar
    Hartford, Juliet
    Khristov, Vladimir
    Dejene, Roba
    Chang, Justin
    Patnaik, Sarita
    Lu, Quanlong
    Banerjee, Poulomi
    Silver, Jason
    Kettenhofen, Christine
    Patel, Dishita
    Lotfi, Mostafa
    Malicdan, May
    Hotaling, Nathan
    Maminishkis, Arvydas
    Sridharan, Rupa
    Brooks, Brian
    Miyagishima, Kiyoharu
    Gunay-Aygun, Meral
    Pal, Rajarshi
    Westlake, Christopher
    Miller, Sheldon
    Sharma, Ruchi
    Bharti, Kapil

  2. Author Address

    Institute of Molecular Physiology, Johannes-Gutenberg University, Mainz, Germany., National Eye Institute, NIH, Bethesda, MD, USA., National Cancer Institute, NIH, Frederick, MD, USA., School of Regenerative Medicine, Manipal University, Bangalore, India., National Human Genome Research Institute, NIH, Bethesda, MD, USA., University of Wisconsin, Madison, WI, USA., National Eye Institute, NIH, Bethesda, MD, USA. Electronic address: kapilbharti@mail.nih.gov.,
    1. Year: 2018
    2. Date: Jan 02
  2. Journal: Cell reports
    1. 22
    2. 1
    3. Pages: 189-205
  4. Type of Article: Article
  5. ISSN: 2211-1247
  1. Abstract:

    Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells. In contrast, ciliopathy patient-derived iPSC-RPE and iPSC-RPE with a knockdown of ciliary-trafficking protein remain immature, with defective apical processes, reduced functionality, and reduced adult-specific gene expression. Proteins of the primary cilium regulate RPE maturation by simultaneously suppressing canonical WNT and activating PKCd pathways. A similar cilium-dependent maturation pathway exists in lung epithelium. Our results provide insights into ciliopathy-induced retinal degeneration, demonstrate a developmental role for primary cilia in epithelial maturation, and provide a method to mature iPSC epithelial cells for clinical applications. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2017.12.038
  3. PMID: 29298421
  4. View record in Web of Science®
  5. WOS: 000419131600017
  6. PII : S2211-1247(17)31847-8

Library Notes

  1. Fiscal Year: FY2017-2018
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