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Irina I Nagy, Qi Xu, Florence Naillat, Nsrein Ali, Ilkka Miinalainen, Anatoly Samoylenko, Seppo J Vainio
BACKGROUND: Wnt11 is a member of the Wnt family of secreted signals controlling the early steps in ureteric bud (UB) branching. Due to the reported lethality of Wnt11 knockout embryos in utero, its role in later mammalian kidney organogenesis remains open. The presence of Wnt11 in the emerging tubular system suggests that it may have certain roles later in the development of the epithelial ductal system. RESULTS: The Wnt11 knockout allele was backcrossed with the C57Bl6 strain for several generations to address possible differences in penetrance of the kidney phenotypes...
2016: BMC Developmental Biology
Peng Cheng, Jia Wang, Indrayani Waghmare, Stefania Sartini, Vito Coviello, Sunghak Kim, Ahmed Mohyeldin, Marat S Pavlyukov, Zhuo Zhang, Mutsuko Minata, Claudia L L Valentim, Rishi Raj Chhipa, Krishna P L Bhat, Biplab Dasgupta, Concettina La Motta, Madhuri Kango-Singh, Ichiro Nakano
Glioma stem-like cells (GSC) with tumor initiating activity orchestrate the cellular hierarchy in glioblastoma (GBM) and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1-ALDH1A3 signaling axis as a determinant of the MES GSC phenotype. The transcription factor FOXD1 is expressed predominantly in patient-derived cultures enriched with MES, but not with the proneural (PN) GSC subtype...
August 28, 2016: Cancer Research
Hock Chuan Yeo, Sherwin Ting, Romulo Martin Brena, Geoffrey Koh, Allen Chen, Siew Qi Toh, Yu Ming Lim, Steve Kah Weng Oh, Dong-Yup Lee
The differentiation efficiency of human embryonic stem cells (hESCs) into heart muscle cells (cardiomyocytes) is highly sensitive to culture conditions. To elucidate the regulatory mechanisms involved, we investigated hESCs grown on three distinct culture platforms: feeder-free Matrigel, mouse embryonic fibroblast feeders, and Matrigel replated on feeders. At the outset, we profiled and quantified their differentiation efficiency, transcriptome, transcription factor binding sites and DNA-methylation. Subsequent genome-wide analyses allowed us to reconstruct the relevant interactome, thereby forming the regulatory basis for implicating the contrasting differentiation efficiency of the culture conditions...
2016: Scientific Reports
Juan Chen, Zhenwen Qian, Fengling Li, Jinzhi Li, Yi Lu
Background/Aims: The integration of multiple profiling data and the construction of a transcriptional regulatory network may provide additional insights into the molecular mechanisms of hepatocellular carcinoma (HCC). The present study was conducted to investigate the deregulation of genes and the transcriptional regulatory network in HCC. Methods: An integrated analysis of HCC gene expression datasets was performed in Gene Expression Omnibus. Functional annotation of the differentially expression genes (DEGs) was conducted...
July 27, 2016: Gut and Liver
Guangzhong Xu, Kai Li, Nengwei Zhang, Bin Zhu, Guosheng Feng
Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer. Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed. Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs...
2016: Gastroenterology Research and Practice
Dario R Lemos, Graham Marsh, Angela Huang, Gabriela Campanholle, Takahide Aburatani, Lan Dang, Ivan G Gomez, Ken Fisher, Giovanni Ligresti, Janos Peti-Peterdi, Jeremy S Duffield
Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature, that have been shown to participate in tissue regeneration. Here we tested the hypothesis that kidney pericytes derived from FoxD1+ mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, BUN and albuminuria within 96h indicated acute kidney injury in pericyte-ablated mice...
June 22, 2016: American Journal of Physiology. Renal Physiology
Artur Brandt, Katharina Löhers, Manfred Beier, Barbara Leube, Carmen de Torres, Jaume Mora, Parineeta Arora, Parmjit S Jat, Brigitte Royer-Pokora
We describe a stromal predominant Wilms tumor with focal anaplasia and a complex, tumor specific chromosome 11 aberration: a homozygous deletion of the entire WT1 gene within a heterozygous 11p13 deletion and an additional region of uniparental disomy (UPD) limited to 11p15.5-p15.2 including the IGF2 gene. The tumor carried a heterozygous p.T41A mutation in CTNNB1. Cells established from the tumor carried the same chromosome 11 aberration, but a different, homozygous p.S45Δ CTNNB1 mutation. Uniparental disomy (UPD) 3p21...
2016: PloS One
Roel Bijkerk, Ruben G de Bruin, Coen van Solingen, Janine M van Gils, Jacques M G J Duijs, Eric P van der Veer, Ton J Rabelink, Benjamin D Humphreys, Anton Jan van Zonneveld
Chronic kidney disease is associated with progressive renal fibrosis, where perivascular cells give rise to the majority of α-smooth muscle actin (α-SMA) positive myofibroblasts. Here we sought to identify pericytic miRNAs that could serve as a target to decrease myofibroblast formation. Kidney fibrosis was induced in FoxD1-GC;Z/Red-mice by unilateral ureteral obstruction followed by FACS sorting of dsRed-positive FoxD1-derivative cells and miRNA profiling. MiR-132 selectively increased 21-fold during pericyte-to-myofibroblast formation, whereas miR-132 was only 2...
June 2016: Kidney International
Jessica K Edwards
No abstract text is available yet for this article.
June 2016: Nature Reviews. Nephrology
Hanako Kobayashi, Qingdu Liu, Thomas C Binns, Andres A Urrutia, Olena Davidoff, Pinelopi P Kapitsinou, Andrew S Pfaff, Hannes Olauson, Annika Wernerson, Agnes B Fogo, Guo-Hua Fong, Kenneth W Gross, Volker H Haase
Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear...
May 2, 2016: Journal of Clinical Investigation
Daniela Fanni, Clara Gerosa, Laura Vinci, Rossano Ambu, Angelica Dessì, Peter Van Eyken, Vassilios Fanos, Gavino Faa
In recent years, the renal interstitium has been identified as the site of multiple cell types, giving rise to multiple contiguous cellular networks with multiple fundamental structural and functional roles. Few studies have been carried out on the morphological and functional properties of the stromal/interstitial renal cells during the intrauterine life. This work was aimed at reviewing the peculiar features of renal interstitial stem/progenitor cells involved in kidney development. The origin of the renal interstitial progenitor cells remains unknown...
December 2016: Journal of Maternal-fetal & Neonatal Medicine
Tomoko Ohmori, Shunsuke Tanigawa, Yusuke Kaku, Sayoko Fujimura, Ryuichi Nishinakamura
The mammalian kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud, the former of which contains nephron progenitors. The third lineage, the stroma, fills up the interstitial space and is derived from distinct progenitors that express the transcription factor Foxd1. We showed previously that deletion of the nuclear factor Sall1 in nephron progenitors leads to their depletion in mice. However, Sall1 is expressed not only in nephron progenitors but also in stromal progenitors...
2015: Scientific Reports
Kathie-Anne Walters, Rachael Olsufka, Rolf E Kuestner, Xiagang Wu, Kai Wang, Shawn J Skerrett, Adrian Ozinsky
BACKGROUND: Francisella infection attenuates immune cell infiltration and expression of selected pro-inflammatory cytokines in response to endogenous LPS, suggesting the bacteria is actively antagonizing at least some part of the response to Toll-like receptor 4 (TLR4) engagement. The ability of different Francisella strains to inhibit the ability of E. coli LPS to induce a pulmonary inflammatory response, as measured by gene expression profiling, was examined to define the scope of modulation and identify of inflammatory genes/pathways that are specifically antagonized by a virulent F...
2015: BMC Genomics
Yu Leng Phua, Jessica Y S Chu, April K Marrone, Andrew J Bodnar, Sunder Sims-Lucas, Jacqueline Ho
MicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA levels. While previous studies have demonstrated that miRNAs are indispensable in the nephron progenitor and ureteric bud lineage, little is understood about stromal miRNAs during kidney development. The renal stroma (marked by expression of FoxD1) gives rise to the renal interstitium, a subset of peritubular capillaries, and multiple supportive vascular cell types including pericytes and the glomerular mesangium. In this study, we generated FoxD1(GC);Dicer(fl/fl) transgenic mice that lack miRNA biogenesis in the FoxD1 lineage...
October 2015: Physiological Reports
Ivan G Gomez, Jeremy S Duffield
Recent studies have identified a poorly appreciated yet extensive population of perivascular mesenchymal cells in the kidney, which are derived from metanephric mesenchyme progenitor cells during nephrogenesis at which time they express the transcription factor FOXD1. Some studies have called these resident fibroblasts, whereas others have called them pericytes. Regardless of nomenclature, many are partially integrated into the capillary basement membrane and contribute in important ways to the homeostasis of peritubular capillaries...
November 2014: Kidney International Supplements
Maria Luisa S Sequeira-Lopez, Vidya K Nagalakshmi, Minghong Li, Curt D Sigmund, R Ariel Gomez
Renin, the key regulated enzyme of the renin-angiotensin system regulates blood pressure, fluid-electrolyte homeostasis, and renal morphogenesis. Whole body deletion of the renin gene results in severe morphological and functional derangements, including thickening of renal arterioles, hydronephrosis, and inability to concentrate the urine. Because renin is found in vascular and tubular cells, it has been impossible to discern the relative contribution of tubular versus vascular renin to such a complex phenotype...
September 15, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Sohei Nakayama, Kenzo Soejima, Hiroyuki Yasuda, Satoshi Yoda, Ryosuke Satomi, Shinnosuke Ikemura, Hideki Terai, Takashi Sato, Norihiro Yamaguchi, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Keiko Ohgino, Katsuhiko Naoki, Tomoko Betsuyaku
AIM: Clinical microarray datasets were analyzed to search for new therapeutic targets and prognostic markers of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Microarray datasets from 90 lung cancer specimens, were analyzed with focus on the FOXD1 gene. Levels of FOXD1 mRNA were assessed in lung cancer cell lines and these levels were correlated with survival. RESULTS: FOXD1-knockdown led to suppression of cell proliferation. Moreover, patients with high FOXD1 expression survived for a significantly shorter time than those with low FOXD1 expression...
January 2015: Anticancer Research
Yi-Fan Zhao, Jing-Yu Zhao, Hong Yue, Ke-Shi Hu, Hao Shen, Zheng-Gang Guo, Xiao-Jun Su
Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. As a member of the forkhead family, FOXD1 is required during kidney development and its inactivation results in failure of nephron progenitor cells. However, the role of FOXD1 in carcinogenesis and progression is still limited. Here, we reported that FOXD1 is a potential oncogene in breast cancer. We found that FOXD1 is up-regulated in breast cancer tissues. Depletion of FOXD1 expression decreases the ability of cell proliferation and chemoresistance in MDA-MB-231 cells, whereas overexpression of FOXD1 increases the ability of cell proliferation and chemoresistance in MCF-7 cells...
January 2, 2015: Biochemical and Biophysical Research Communications
Maria Luisa S Sequeira-Lopez, Eugene E Lin, Minghong Li, Yan Hu, Curt D Sigmund, R Ariel Gomez
The development of the kidney arterioles is poorly understood. Mature arterioles contain several functionally and morphologically distinct cell types, including smooth muscle, endothelial, and juxtaglomerular cells, and they are surrounded by interconnected pericytes, fibroblasts, and other interstitial cells. We have shown that the embryonic kidney possesses all of the necessary precursors for the development of the renal arterial tree, and those precursors assemble in situ to form the kidney arterioles. However, the identity of those precursors was unclear...
January 15, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Akio Kobayashi, Joshua W Mugford, A Michaela Krautzberger, Natalie Naiman, Jessica Liao, Andrew P McMahon
The mammalian kidney is a complex organ consisting of multiple cell types. We previously showed that the Six2-expressing cap mesenchyme is a multipotent self-renewing progenitor population for the main body of the nephron, the basic functional unit of the kidney. However, the cellular mechanisms establishing stromal tissues are less clear. We demonstrate that the Foxd1-expressing cortical stroma represents a distinct multipotent self-renewing progenitor population that gives rise to stromal tissues of the interstitium, mesangium, and pericytes throughout kidney organogenesis...
October 14, 2014: Stem Cell Reports
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