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TRRAP is a central regulator of human multiciliated cell formation.

The Journal of cell biology | 2018

The multiciliated cell (MCC) is an evolutionarily conserved cell type, which in vertebrates functions to promote directional fluid flow across epithelial tissues. In the conducting airway, MCCs are generated by basal stem/progenitor cells and act in concert with secretory cells to perform mucociliary clearance to expel pathogens from the lung. Studies in multiple systems, including Xenopus laevis epidermis, murine trachea, and zebrafish kidney, have uncovered a transcriptional network that regulates multiple steps of multiciliogenesis, ultimately leading to an MCC with hundreds of motile cilia extended from their apical surface, which beat in a coordinated fashion. Here, we used a pool-based short hairpin RNA screening approach and identified TRRAP, an essential component of multiple histone acetyltransferase complexes, as a central regulator of MCC formation. Using a combination of immunofluorescence, signaling pathway modulation, and genomic approaches, we show that (a) TRRAP acts downstream of the Notch2-mediated basal progenitor cell fate decision and upstream of Multicilin to control MCC differentiation; and (b) TRRAP binds to the promoters and regulates the expression of a network of genes involved in MCC differentiation and function, including several genes associated with human ciliopathies.

Pubmed ID: 29588376 RIS Download

Associated grants

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BioLegend (tool)

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This polyclonal targets TRRAP antibody - ChIP Grade

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Anti-TRRAP antibody produced in rabbit (antibody)

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Mucin 5B (H-300) (antibody)

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Acetylated Tubulin (antibody)

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Anti-FOXJ1 antibody produced in rabbit (antibody)

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This unknown targets Forkhead box protein J1 recombinant protein epitope signature tag

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Anti-TRRAP antibody produced in rabbit (antibody)

RRID:AB_10672508

This polyclonal targets TRRAP antibody produced in rabbit

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Purified anti-p63 (?N) (antibody)

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Mucin 5B (H-300) (antibody)

RRID:AB_2282256

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Acetylated Tubulin (antibody)

RRID:AB_609894

This monoclonal targets derived from the hybridoma 6-11B-1 produced by the fusion of mouse myeloma cells and splenocytes from a mouse immunized with acetylated tubulin from the outer arm of Strongylocentrotus purpuratus (sea urchin).

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TRRAP antibody - ChIP Grade (antibody)

RRID:AB_10672042

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TRRAP antibody - ChIP Grade (antibody)

RRID:AB_10672042

This polyclonal targets TRRAP antibody - ChIP Grade

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