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• W4210366498 abstract "Key points The carotid body is a peripheral arterial chemoreceptor that regulates ventilation in response to both acute and sustained hypoxia. Type I cells in this organ respond to low oxygen both acutely by depolarization and dense core vesicle secretion and, over the longer term, via cellular proliferation and enhanced ventilatory responses. Using lineage analysis, the present study shows that the Type I cell lineage itself proliferates and expands in response to sustained hypoxia. Inactivation of HIF‐2α in Type I cells impairs the ventilatory, proliferative and cell intrinsic (dense core vesicle) responses to hypoxia. Inactivation of PHD2 in Type I cells induces multilineage hyperplasia and ultrastructural changes in dense core vesicles to form paraganglioma‐like carotid bodies. These changes, similar to those observed in hypoxia, are dependent on HIF‐2α. Taken together, these findings demonstrate a key role for the PHD2–HIF‐2α couple in Type I cells with respect to the oxygen sensing functions of the carotid body. Abstract The carotid body is a peripheral chemoreceptor that plays a central role in mammalian oxygen homeostasis. In response to sustained hypoxia, it manifests a rapid cellular proliferation and an associated increase in responsiveness to hypoxia. Understanding the cellular and molecular mechanisms underlying these processes is of interest both to specialized chemoreceptive functions of that organ and, potentially, to the general physiology and pathophysiology of cellular hypoxia. We have combined cell lineage tracing technology and conditionally inactivated alleles in recombinant mice to examine the role of components of the HIF hydroxylase pathway in specific cell types within the carotid body. We show that exposure to sustained hypoxia (10% oxygen) drives rapid expansion of the Type I, tyrosine hydroxylase expressing cell lineage, with little transdifferentiation to (or from) that lineage. Inactivation of a specific HIF isoform, HIF‐2α, in the Type I cells was associated with a greatly reduced proliferation of Type I cells and hypoxic ventilatory responses, with ultrastructural evidence of an abnormality in the action of hypoxia on dense core secretory vesicles. We also show that inactivation of the principal HIF prolyl hydroxylase PHD2 within the Type I cell lineage is sufficient to cause multilineage expansion of the carotid body, with characteristics resembling paragangliomas. These morphological changes were dependent on the integrity of HIF‐2α. These findings implicate specific components of the HIF hydroxylase pathway (PHD2 and HIF‐2α) within Type I cells of the carotid body with respect to the oxygen sensing and adaptive functions of that organ." @default.
• W4210366498 created "2022-02-08" @default.
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• W4210366498 date "2018-08-19" @default.
• W4210366498 modified "2023-10-16" @default.
• W4210366498 title "PHD2 inactivation in Type I cells drives HIF‐2α‐dependent multilineage hyperplasia and the formation of paraganglioma‐like carotid bodies" @default.
• W4210366498 cites W1572904226 @default.
• W4210366498 cites W1602845909 @default.
• W4210366498 cites W1744173909 @default.
• W4210366498 cites W1797434159 @default.
• W4210366498 cites W1919120316 @default.
• W4210366498 cites W1949115396 @default.
• W4210366498 cites W1969269984 @default.
• W4210366498 cites W1969734439 @default.
• W4210366498 cites W1974177884 @default.
• W4210366498 cites W1975157300 @default.
• W4210366498 cites W1981557108 @default.
• W4210366498 cites W1991421091 @default.
• W4210366498 cites W1996246227 @default.
• W4210366498 cites W2002196079 @default.
• W4210366498 cites W2005868568 @default.
• W4210366498 cites W2008420683 @default.
• W4210366498 cites W2008430621 @default.
• W4210366498 cites W2016075796 @default.
• W4210366498 cites W2016160962 @default.
• W4210366498 cites W2017575850 @default.
• W4210366498 cites W2020322974 @default.
• W4210366498 cites W2020688747 @default.
• W4210366498 cites W2027398510 @default.
• W4210366498 cites W2027512930 @default.
• W4210366498 cites W2032305338 @default.
• W4210366498 cites W2032984825 @default.
• W4210366498 cites W2035485135 @default.
• W4210366498 cites W2037640272 @default.
• W4210366498 cites W2038253875 @default.
• W4210366498 cites W2039634930 @default.
• W4210366498 cites W2044257922 @default.
• W4210366498 cites W2046369421 @default.
• W4210366498 cites W2047277170 @default.
• W4210366498 cites W2058046363 @default.
• W4210366498 cites W2063552704 @default.
• W4210366498 cites W2064779119 @default.
• W4210366498 cites W2067115931 @default.
• W4210366498 cites W2075278882 @default.
• W4210366498 cites W2077701967 @default.
• W4210366498 cites W2084274356 @default.
• W4210366498 cites W2084913512 @default.
• W4210366498 cites W2085715886 @default.
• W4210366498 cites W2093776019 @default.
• W4210366498 cites W2104135721 @default.
• W4210366498 cites W2108601997 @default.
• W4210366498 cites W2113568840 @default.
• W4210366498 cites W2120053783 @default.
• W4210366498 cites W2120657231 @default.
• W4210366498 cites W2122533794 @default.
• W4210366498 cites W2136023563 @default.
• W4210366498 cites W2136589043 @default.
• W4210366498 cites W2140976529 @default.
• W4210366498 cites W2141410846 @default.
• W4210366498 cites W2142033642 @default.
• W4210366498 cites W2147891751 @default.
• W4210366498 cites W2149472502 @default.
• W4210366498 cites W2163576640 @default.
• W4210366498 cites W2166228256 @default.
• W4210366498 cites W2169516568 @default.
• W4210366498 cites W2173975190 @default.
• W4210366498 cites W2286574444 @default.
• W4210366498 cites W2291336299 @default.
• W4210366498 cites W2603031301 @default.
• W4210366498 cites W2734036824 @default.
• W4210366498 cites W2735380392 @default.
• W4210366498 cites W2778771081 @default.
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• W4210366498 doi "https://doi.org/10.1113/jp275996" @default.
• W4210366498 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29917232" @default.
• W4210366498 hasPublicationYear "2018" @default.
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