The Experts below are selected from a list of 1983 Experts worldwide ranked by ideXlab platform
Saul Suster - One of the best experts on this subject based on the ideXlab platform.
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sclerosing paraganglioma report of 19 cases of an unusual variant of neuroendocrine tumor that may be mistaken for an aggressive malignant neoplasm
The American Journal of Surgical Pathology, 2006Co-Authors: Jose A. Plaza, Paul E Wakely, Christopher D M Fletcher, Cesar A. Moran, Saul SusterAbstract:: Nineteen cases of a distinctive variant of paraganglioma characterized by extensive collagen deposition resulting in a pattern of growth that resembled an invasive malignant neoplasm are described. The patients were 3 men and 16 women, 32 to 69 years of age (mean, 50.5 years). The tumors were located in the carotid body region, parapharyngeal region, and mediastinum. Tumor size ranged from 2 to 6 cm in greatest diameter. Grossly, the tumors were described as rubbery to firm, tan-red, and with extensive areas of sclerosis. Histologic examination showed nests and cords of tumor Cells separated by broad bands of fibrous tissue. The tumor Cells ranged from round to polygonal with abundant cytoplasm to elongated spindle Cells with scant cytoplasm. Nuclear cytomegaly was present focally enhancing the atypical appearance of the tumor Cell population in 17 cases. Mitoses were sparse (<1 x 10 HPF), and there was no evidence of necrosis in any of the cases. Foci of vascular and perineural invasion were present in 2 and 4 cases, respectively. The most striking morphologic feature was the presence of irregular cords and bands of hyalinized fibrous tissue that compartmentalized the lesion into irregular nests, islands, or cords of tumor Cells, imparting them with an infiltrative appearance. All the tumors showed positive immunostaining for chromogranin, synaptophysin, and monoclonal neuron specific enolase. S-100 protein stains identified a Sustentacular Cell network, whereas cytokeratin AE1/AE3 was negative in all cases. Clinical follow-up in 14 cases, ranging from 2 months to 20 years (mean follow-up, 6.6 years) showed evidence of local recurrence in 2 cases and the development of a separate tumor in the contralateral neck in 1 case. The remainder of patients were free of recurrence or metastasis following simple local excision. Because of the prominent sclerosis, a diagnosis of an invasive malignant neoplasm was initially considered in the majority of cases. Sclerosing paraganglioma should be included in the differential diagnosis of sclerosing lesions of the head and neck region and mediastinum. Appropriate immunohistochemical stains may be of aid for establishing the correct diagnosis.
Jeffrey R Martens - One of the best experts on this subject based on the ideXlab platform.
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primary cilia on horizontal basal Cells regulate regeneration of the olfactory epithelium
The Journal of Neuroscience, 2015Co-Authors: Ariell M Joiner, James E. Schwob, Warren W Green, Jeremy C Mcintyre, Benjamin L Allen, Jeffrey R MartensAbstract:The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple Cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem Cells, frequently dividing globose basal Cells and quiescent horizontal basal Cells (HBCs). However, the precise mechanisms by which these Cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem Cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to Sustentacular Cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, Cell type-specific Ift88 knock-out mouse line ( K5rtTA;tetOCre;Ift88fl/fl ) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation. SIGNIFICANCE STATEMENT We show for the first time the presence of primary cilia on a quiescent population of basal stem Cells, the horizontal basal Cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory neurons and may include alterations in OE maintenance and regeneration.
Jose A. Plaza - One of the best experts on this subject based on the ideXlab platform.
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sclerosing paraganglioma report of 19 cases of an unusual variant of neuroendocrine tumor that may be mistaken for an aggressive malignant neoplasm
The American Journal of Surgical Pathology, 2006Co-Authors: Jose A. Plaza, Paul E Wakely, Christopher D M Fletcher, Cesar A. Moran, Saul SusterAbstract:: Nineteen cases of a distinctive variant of paraganglioma characterized by extensive collagen deposition resulting in a pattern of growth that resembled an invasive malignant neoplasm are described. The patients were 3 men and 16 women, 32 to 69 years of age (mean, 50.5 years). The tumors were located in the carotid body region, parapharyngeal region, and mediastinum. Tumor size ranged from 2 to 6 cm in greatest diameter. Grossly, the tumors were described as rubbery to firm, tan-red, and with extensive areas of sclerosis. Histologic examination showed nests and cords of tumor Cells separated by broad bands of fibrous tissue. The tumor Cells ranged from round to polygonal with abundant cytoplasm to elongated spindle Cells with scant cytoplasm. Nuclear cytomegaly was present focally enhancing the atypical appearance of the tumor Cell population in 17 cases. Mitoses were sparse (<1 x 10 HPF), and there was no evidence of necrosis in any of the cases. Foci of vascular and perineural invasion were present in 2 and 4 cases, respectively. The most striking morphologic feature was the presence of irregular cords and bands of hyalinized fibrous tissue that compartmentalized the lesion into irregular nests, islands, or cords of tumor Cells, imparting them with an infiltrative appearance. All the tumors showed positive immunostaining for chromogranin, synaptophysin, and monoclonal neuron specific enolase. S-100 protein stains identified a Sustentacular Cell network, whereas cytokeratin AE1/AE3 was negative in all cases. Clinical follow-up in 14 cases, ranging from 2 months to 20 years (mean follow-up, 6.6 years) showed evidence of local recurrence in 2 cases and the development of a separate tumor in the contralateral neck in 1 case. The remainder of patients were free of recurrence or metastasis following simple local excision. Because of the prominent sclerosis, a diagnosis of an invasive malignant neoplasm was initially considered in the majority of cases. Sclerosing paraganglioma should be included in the differential diagnosis of sclerosing lesions of the head and neck region and mediastinum. Appropriate immunohistochemical stains may be of aid for establishing the correct diagnosis.
James E. Schwob - One of the best experts on this subject based on the ideXlab platform.
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Notch1 maintains dormancy of olfactory horizontal basal Cells, a reserve neural stem Cell
Proceedings of the National Academy of Sciences, 2017Co-Authors: Daniel B. Herrick, Brian Lin, Jesse Peterson, Nikolai Schnittke, James E. SchwobAbstract:The remarkable capacity of the adult olfactory epithelium (OE) to regenerate fully both neurosensory and nonneuronal Cell types after severe epithelial injury depends on life-long persistence of two stem Cell populations: the horizontal basal Cells (HBCs), which are quiescent and held in reserve, and mitotically active globose basal Cells. It has recently been demonstrated that down-regulation of the ΔN form of the transcription factor p63 is both necessary and sufficient to release HBCs from dormancy. However, the mechanisms by which p63 is down-regulated after acute OE injury remain unknown. To identify the Cellular source of potential signaling mechanisms, we assessed HBC activation after neuron-only and Sustentacular Cell death. We found that ablation of Sustentacular Cells is sufficient for HBC activation to multipotency. By expression analysis, next-generation sequencing, and immunohistochemical examination, down-regulation of Notch pathway signaling is coincident with HBC activation. Therefore, using HBC-specific conditional knockout of Notch receptors and overexpression of N1ICD, we show that Notch signaling maintains p63 levels and HBC dormancy, in contrast to its suppression of p63 expression in other tissues. Additionally, Notch1, but not Notch2, is required to maintain HBC dormancy after selective neuronal degeneration. Taken together, our data indicate that the activation of HBCs observed after tissue injury or Sustentacular Cell ablation is caused by the reduction/elimination of Notch signaling on HBCs; elimination of Jagged1 expressed by Sustentacular Cells may be the ligand responsible.
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primary cilia on horizontal basal Cells regulate regeneration of the olfactory epithelium
The Journal of Neuroscience, 2015Co-Authors: Ariell M Joiner, James E. Schwob, Warren W Green, Jeremy C Mcintyre, Benjamin L Allen, Jeffrey R MartensAbstract:The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple Cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem Cells, frequently dividing globose basal Cells and quiescent horizontal basal Cells (HBCs). However, the precise mechanisms by which these Cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem Cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to Sustentacular Cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, Cell type-specific Ift88 knock-out mouse line ( K5rtTA;tetOCre;Ift88fl/fl ) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation. SIGNIFICANCE STATEMENT We show for the first time the presence of primary cilia on a quiescent population of basal stem Cells, the horizontal basal Cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory neurons and may include alterations in OE maintenance and regeneration.
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Nonintegrin laminin receptor precursor protein is expressed on olfactory stem and progenitor Cells.
The Journal of Comparative Neurology, 2007Co-Authors: Woochan Jang, Kwang Pyo Kim, James E. SchwobAbstract:The biochemical identification and immunocytochemical characterization of a Cell surface antigen, expressed on globose basal Cells (GBCs) of the rodent olfactory epithelium (OE), are described. The monoclonal antibody (MAb) GBC-3 recognizes a surface protein, confirmed by both live Cell staining and fluorescence-activated Cell sorting. Two-dimensional SDS-PAGE/Western blot followed by tandem mass spectrometry demonstrates that the Cell surface GBC-3 antigen is the 40 kDa laminin receptor precursor protein. The MAb GBC-3 labels the vast majority of Cells among the GBC population and does not stain either Sustentacular Cells or horizontal basal Cells (HBCs) in the normal rat OE. After epithelial lesion by exposure to methyl bromide, the remaining Cells, which are mostly GBCs, are heavily stained by GBC-3, and colabeled with GBC-3 and Sustentacular Cell or HBC markers. GBC-3 will be a potentially useful tool for identifying and characterizing GBCs.
Paul E Wakely - One of the best experts on this subject based on the ideXlab platform.
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sclerosing paraganglioma report of 19 cases of an unusual variant of neuroendocrine tumor that may be mistaken for an aggressive malignant neoplasm
The American Journal of Surgical Pathology, 2006Co-Authors: Jose A. Plaza, Paul E Wakely, Christopher D M Fletcher, Cesar A. Moran, Saul SusterAbstract:: Nineteen cases of a distinctive variant of paraganglioma characterized by extensive collagen deposition resulting in a pattern of growth that resembled an invasive malignant neoplasm are described. The patients were 3 men and 16 women, 32 to 69 years of age (mean, 50.5 years). The tumors were located in the carotid body region, parapharyngeal region, and mediastinum. Tumor size ranged from 2 to 6 cm in greatest diameter. Grossly, the tumors were described as rubbery to firm, tan-red, and with extensive areas of sclerosis. Histologic examination showed nests and cords of tumor Cells separated by broad bands of fibrous tissue. The tumor Cells ranged from round to polygonal with abundant cytoplasm to elongated spindle Cells with scant cytoplasm. Nuclear cytomegaly was present focally enhancing the atypical appearance of the tumor Cell population in 17 cases. Mitoses were sparse (<1 x 10 HPF), and there was no evidence of necrosis in any of the cases. Foci of vascular and perineural invasion were present in 2 and 4 cases, respectively. The most striking morphologic feature was the presence of irregular cords and bands of hyalinized fibrous tissue that compartmentalized the lesion into irregular nests, islands, or cords of tumor Cells, imparting them with an infiltrative appearance. All the tumors showed positive immunostaining for chromogranin, synaptophysin, and monoclonal neuron specific enolase. S-100 protein stains identified a Sustentacular Cell network, whereas cytokeratin AE1/AE3 was negative in all cases. Clinical follow-up in 14 cases, ranging from 2 months to 20 years (mean follow-up, 6.6 years) showed evidence of local recurrence in 2 cases and the development of a separate tumor in the contralateral neck in 1 case. The remainder of patients were free of recurrence or metastasis following simple local excision. Because of the prominent sclerosis, a diagnosis of an invasive malignant neoplasm was initially considered in the majority of cases. Sclerosing paraganglioma should be included in the differential diagnosis of sclerosing lesions of the head and neck region and mediastinum. Appropriate immunohistochemical stains may be of aid for establishing the correct diagnosis.
