The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder

Gevaert, Thomas; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Aa, F. Van Der; Pintelon, Isabel; Timmermans, J.‐P.; Roskams, Tania; Steiner, Clara; Neuhaus, Jochen; Ridder, Dirk De

doi:10.1016/s1569-9056(17)30271-3

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…old male) those cells were filled with lipofuscin granules, which might be a sign of ageing (Fig. C). We did not find c‐kit + interstitial Cells of Cajal (ICCs) in the ULP as recently reported by our group, but the bIC shared some ultrastructural features with ICCs (partly coverage by basal lamina, small cell body, several thick branching processes with mitochondria localized at the branching points). The bIC in our specimen penetrated the BM of the urothelium and made budding contacts to urothelial cells (Fig.…”

Section: Discussionsupporting

confidence: 78%

3D‐electron microscopic characterization of interstitial cells in the human bladder upper lamina propria

Neuhaus

Schröppel

Dass

et al. 2017

Neurourology and Urodynamics

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We furthermore identified one branched cell (bIC) with several processes contacting urothelial cells by penetrating the basal membrane. This cell did not make any contacts to other ICs within the upper lamina propria. We found no evidence for the occurrence of telocytes in the upper lamina propria. Conclusions: Comprehensive 3D-ultrastructural analysis of the human bladder confirmed distinct subtypes of interstitial cells. We provide evidence for a foremost unknown direct connection between a branched interstitial cell and urothelial cells of which the functional role has still to be elucidated. 3D-ultrastructure analyses at high resolution are needed to further define the subpopulations of lamina propria cells and cell-cell interactions. K E Y W O R D S3D-confocal fluorescence imaging, 3D-scanning electron microscopy (SEM), cellular fibronectin EDA domain, connexin 43 (Cx43), Interstitial Cells of Cajal (ICC), telocyte, wheat germ agglutinin (WGA) staining Abbreviations: aSMCA, alpha smooth muscle cell actin; bIC, branched interstitial cell; BL, basal lamina; BM, (urothelial) basal membrane; fIC, fibroblast type interstitial cell; FIB-SEM, focused ion beam scanning electron microscopy; GJ, gap junction; mIC, myoid interstitial cell; rER, rough endoplasmic reticulum; sER, smooth endoplasmic reticulum; UC, urothelial cell; ULP, upper lamina propria.

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Section: Discussionsupporting

confidence: 78%

3D‐electron microscopic characterization of interstitial cells in the human bladder upper lamina propria

Neuhaus

Schröppel

Dass

et al. 2017

Neurourology and Urodynamics

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“…However, a uniquely identifiable ICC in the bladder has not been convincingly characterized 3, 23, 24 . Although Kit (CD117) is the prototypical marker for ICCs in the intestinal tract 25 , recent data suggested mouse bladder Kit is expressed only on mast cells 26 . In our data, Kit expression was restricted to a small number of immune and DSM cells and other gut ICC markers ( Pdgfra , Entpd2 , Cd34 , and Gja1 ) were either absent or not restricted to the fibroblast cluster (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, as opposed to being ICC-like our data indicates this cell type to be closely related to other bladder fibroblasts and forms a continuous fibroblastic network extending from the suburothelium deep into the detrusor. The growth factor receptor Kit marks GI ICCs and its associated antibodies have been used with mixed results to define fibroblast-like ICCs within the bladder 23, 26 . Our data agrees with the absence of Kit expression in the fibroblast/interstitial cell compartment.…”

Section: Discussionmentioning

confidence: 99%

A Cellular Reference Resource for the Mouse Urinary Bladder

Baker

Al-Naggar

Sivajothi

et al. 2021

Preprint

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The urinary bladder functions as a reservoir to store and extrude liquid bodily waste. Significant debate exists as to this tissue's cellular composition and genes associated with their functions. We use a repertoire of cell profiling tools to comprehensively define and spatial resolve cell types. We characterize spatially validated, basal-to-luminal gene expression dynamics within the urothelium, the cellular source of most bladder cancers. We define three distinct populations of fibroblasts that spatially organize from the sub-urothelial layer through to the detrusor muscle, clarifying knowledge around these controversial interstitial cells, and associate increased fibroblasts with aging. We overcome challenges of profiling the detrusor muscle, absence from earlier single cell studies, to report on its transcriptome with many novel and neuronal-like features presumably associated with neuromuscular junctions. Our approach provides a blueprint for tissue atlas construction and the data provides the foundation for future studies of bladder function in health and disease.

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“…C‐KIT, also known as CD117, is a tyrosine‐protein kinase that functions as cell‐surface receptor and plays critical role in regulating cell survival and proliferation, stem cell maintenance, hematopoiesis and migration . Mutations and abnormal expressions of c‐Kit in AML1 have been discussed by previously studies.…”

Section: Introductionmentioning

confidence: 99%

AML1/ETO trans‐activates c‐KIT expression through the long range interaction between promoter and intronic enhancer

Tian¹,

Wang²,

Hu³

et al. 2018

J of Cellular Biochemistry

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The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation.

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The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder

Cited by 3 publications

References 21 publications

3D‐electron microscopic characterization of interstitial cells in the human bladder upper lamina propria

3D‐electron microscopic characterization of interstitial cells in the human bladder upper lamina propria

A Cellular Reference Resource for the Mouse Urinary Bladder

AML1/ETO trans‐activates c‐KIT expression through the long range interaction between promoter and intronic enhancer

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