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https://www.readbyqxmd.com/read/29771971/constitutive-metanephric-mesenchyme-specific-expression-of-interferon-gamma-causes-renal-dysplasia-by-regulating-sall1-expression
#1
Kangsun Yun, Arthur A Hurwitz, Alan O Perantoni
Transplacental viral and parasitic infections have been shown to initiate an innate response in the mammalian embryo by increasing the expression of pro-inflammatory cytokines such as interferon-gamma (Ifng). However, the developmental consequences of an activated innate immunity and, in particular, the effects of induction of Ifng expression independent of infection have been largely overlooked. Here, we demonstrate in vivo that the conditional overexpression of Ifng in metanephric mesenchymal (MM) progenitors results in renal agenesis or hypoplasia...
2018: PloS One
https://www.readbyqxmd.com/read/29721946/sall1-regulates-microglial-morphology-cell-autonomously-in-the-developing-retina
#2
Hideto Koso, Ryuichi Nishinakamura, Sumiko Watanabe
Retinal degeneration often accompanies microglial activation and infiltration of monocyte-derived macrophages into the retina, resulting in the coexistence of microglia and monocyte-derived macrophages in the retina. We previously showed that the Sall1 zinc-finger transcriptional factor is expressed specifically in microglia within the retinal phagocyte pool, and analyses of Sall1 knockout mice revealed that microglial morphology changed from a ramified to a more amoeboid appearance in the developing retina...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29712641/histone-deacetylases-1-and-2-regulate-the-transcriptional-programs-of-nephron-progenitors-and-renal-vesicles
#3
Hongbing Liu, Shaowei Chen, Xiao Yao, Yuwen Li, Chao-Hui Chen, Jiao Liu, Zubaida Saifudeen, Samir S El-Dahr
Nephron progenitor cells (NPC) are Six2-positive metanephric mesenchyme cells, which undergo self-renewal and differentiation to give rise to nephrons until the end of nephrogenesis. HDACs are a group of epigenetic regulators that control cell fate but their role in balancing NPC renewal and differentiation is unknown. Here, we report that NPC-specific deletion of HDAC1 and HDAC2 genes in mice results in early postnatal lethality due to renal hypo-dysplasia and loss of NPC. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer...
April 30, 2018: Development
https://www.readbyqxmd.com/read/29695308/the-presence-of-human-mesenchymal-stem-cells-of-renal-origin-in-amniotic-fluid-increases-with-gestational-time
#4
Md Shaifur Rahman, Lucas-Sebastian Spitzhorn, Wasco Wruck, Carsten Hagenbeck, Percy Balan, Nina Graffmann, Martina Bohndorf, Audrey Ncube, Pascale V Guillot, Tanja Fehm, James Adjaye
BACKGROUND: Established therapies for managing kidney dysfunction such as kidney dialysis and transplantation are limited due to the shortage of compatible donated organs and high costs. Stem cell-based therapies are currently under investigation as an alternative treatment option. As amniotic fluid is composed of fetal urine harboring mesenchymal stem cells (AF-MSCs), we hypothesized that third-trimester amniotic fluid could be a novel source of renal progenitor and differentiated cells...
April 25, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29625565/sall1-functions-as-a-tumor-suppressor-in-breast-cancer-by-regulating-cancer-cell-senescence-and-metastasis-through-the-nurd-complex
#5
Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C Hsueh, Lynn Robbins, Susan M Kiefer, Yanping Zhang, Pamela Hunborg, Mark A Varvares, Michael Rauchman, Guangyong Peng
BACKGROUND: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown. METHODS: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate...
April 6, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29602211/genetic-effects-of-the-transcription-factors-sal-like-1-and-spalt-like-transcription-factor-3-on-egg-production-related-traits-in-chinese-dagu-hens
#6
Hongyan Zhu, Ning Qin, Thobela Louis Tyasi, Yang Jing, Dehui Liu, Shuguo Yuan, Rifu Xu
Transcription factors (TFs) encoded by SALL1 and SALL3 genes play central roles in the regulation of ovarian development in hens. The present study aimed to examine polymorphisms of these two genes in Chinese Dagu chickens, and to identify the effects of TFs on the laying performance. Among the population, two novel single-nucleotide polymorphisms (SNPs) were identified by single-strand conformation polymorphism (SSCP) in the amplicons of the candidate genes. The effect of the SNP (729C > A) in exon 2 of SALL1 gene on egg production at 43, 57, and 66 weeks and EW at 30 and 43 weeks were the most significant in the 360 samples (P < 0...
March 30, 2018: Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
https://www.readbyqxmd.com/read/29581773/epigenetic-modification-of-sall1-as-a-novel-biomarker-for-the-prognosis-of-early-stage-head-and-neck-cancer
#7
Kiyoshi Misawa, Yuki Misawa, Atsushi Imai, Daiki Mochizuki, Shiori Endo, Masato Mima, Ryuji Ishikawa, Hideya Kawasaki, Takashi Yamatodani, Takeharu Kanazawa
This study examined Sal-like protein ( SALL)1 methylation profiles in head and neck squamous-cell carcinoma (HNSCC) patients at diagnosis and follow-up, and evaluated their prognostic significance and value as a biomarker. SALL1 expression was examined in a panel of cell lines by quantitative reverse transcription PCR (qRT-PCR). Promoter methylation was determined by quantitative methylation-specific polymerase chain reaction (qMSP) and was compared to the clinical characteristics of 205 samples. SALL1 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 31...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29511085/sal-like-4-protein-levels-in-breast-cancer-cells-are-post-translationally-down-regulated-by-tripartite-motif-containing-21
#8
Junji Itou, Wenzhao Li, Shinji Ito, Sunao Tanaka, Yoshiaki Matsumoto, Fumiaki Sato, Masakazu Toi
Sal-like 4 (SALL4) is a transcription factor that enhances proliferation and migration in breast cancer cells. SALL4 expression therefore has the potential to promote cancer malignancy. However, the regulatory mechanisms involved in SALL4 protein expression have not been thoroughly elucidated. In this study, we observed that treating MCF-7 and SUM159 breast cancer cell lines with a proteasome inhibitor increases SALL4 protein levels, suggesting that SALL4 is degraded by the ubiquitin-proteasome system. Using immunoprecipitation to uncover SALL4-binding proteins, we identified an E3 ubiquitin-protein ligase, tripartite motif-containing 21 (TRIM21)...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29500469/clinically-diverse-phenotypes-and-genotypes-of-patients-with-branchio-oto-renal-syndrome
#9
Ai Unzaki, Naoya Morisada, Kandai Nozu, Ming Juan Ye, Shuichi Ito, Tatsuo Matsunaga, Kenji Ishikura, Shihomi Ina, Koji Nagatani, Takayuki Okamoto, Yuji Inaba, Naoko Ito, Toru Igarashi, Shoichiro Kanda, Ken Ito, Kohei Omune, Takuma Iwaki, Kazuyuki Ueno, Mayumi Yahata, Yasufumi Ohtsuka, Eriko Nishi, Nobuya Takahashi, Tomoaki Ishikawa, Shunsuke Goto, Nobuhiko Okamoto, Kazumoto Iijima
Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchiogenic anomalies, hearing loss, and renal anomalies. The aim of this study was to reveal the clinical phenotypes and their causative genes in Japanese BOR patients. Patients clinically diagnosed with BOR syndrome were analyzed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA), array-based comparative genomic hybridization (aCGH), and next-generation sequencing (NGS). We identified the causative genes in 38/51 patients from 26/36 families; EYA1 aberrations were identified in 22 families, SALL1 mutations were identified in two families, and SIX1 mutations and a 22q partial tetrasomy were identified in one family each...
May 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29484122/-sall1-expression-in-acute-myeloid-leukemia
#10
Huda Salman, Xiao Shuai, Anh Thu Nguyen-Lefebvre, Banabihari Giri, Mingqiang Ren, Michael Rauchman, Lynn Robbins, Wei Hou, Hasan Korkaya, Yupo Ma
Similar signaling pathways could operate in both normal hematopoietic stem and progenitor cells (HSPCs) and leukemia stem cells (LSCs). Thus, targeting LSCs signaling without substantial toxicities to normal HSPCs remains challenging. SALL1, is a member of the transcriptional network that regulates stem cell pluripotency, and lacks significant expression in most adult tissues, including normal bone marrow (NBM). We examined the expression and functional characterization of SALL1 in NBM and in acute myeloid leukemia (AML) using in vitro and in vivo assays...
January 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29395072/truncated-sall1-impedes-primary-cilia-function-in-townes-brocks-syndrome
#11
Laura Bozal-Basterra, Itziar Martín-Ruíz, Lucia Pirone, Yinwen Liang, Jón Otti Sigurðsson, Maria Gonzalez-Santamarta, Immacolata Giordano, Estibaliz Gabicagogeascoa, Angela de Luca, Jose A Rodríguez, Andrew O M Wilkie, Jürgen Kohlhase, Deborah Eastwood, Christopher Yale, Jesper V Olsen, Michael Rauchman, Kathryn V Anderson, James D Sutherland, Rosa Barrio
Townes-Brocks syndrome (TBS) is characterized by a spectrum of malformations in the digits, ears, and kidneys. These anomalies overlap those seen in a growing number of ciliopathies, which are genetic syndromes linked to defects in the formation or function of the primary cilia. TBS is caused by mutations in the gene encoding the transcriptional repressor SALL1 and is associated with the presence of a truncated protein that localizes to the cytoplasm. Here, we provide evidence that SALL1 mutations might cause TBS by means beyond its transcriptional capacity...
February 1, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29377931/transcriptional-regulatory-control-of-mammalian-nephron-progenitors-revealed-by-multi-factor-cistromic-analysis-and-genetic-studies
#12
Lori L O'Brien, Qiuyu Guo, Emad Bahrami-Samani, Joo-Seop Park, Sean M Hasso, Young-Jin Lee, Alan Fang, Albert D Kim, Jinjin Guo, Trudy M Hong, Kevin A Peterson, Scott Lozanoff, Ramya Raviram, Bing Ren, Ben Fogelgren, Andrew D Smith, Anton Valouev, Andrew P McMahon
Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29197384/involvement-of-the-bone-morphogenic-protein-smad-signaling-pathway-in-the-etiology-of-congenital-anomalies-of-the-kidney-and-urinary-tract-accompanied-by-cryptorchidism
#13
Kentaro Mizuno, Akihiro Nakane, Hidenori Nishio, Yoshinobu Moritoki, Hideyuki Kamisawa, Satoshi Kurokawa, Taiki Kato, Ryosuke Ando, Tetsuji Maruyama, Takahiro Yasui, Yutaro Hayashi
BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT), such as renal dysplasia, hydronephrosis, or vesicoureteral reflux, are the most common causes of end-stage renal disease. However, the genetic etiology of CAKUT remains unclear. In this study, we performed whole exome sequencing (WES) to elucidate the genetic etiology of symptomatic CAKUT and CAKUT accompanied by cryptorchidism. METHODS: Three patients with unilateral renal dysplasia accompanied by ipsilateral cryptorchidism were included in this analysis...
December 2, 2017: BMC Urology
https://www.readbyqxmd.com/read/29162051/in-vitro-characterization-of-cd133-lo-cancer-stem-cells-in-retinoblastoma-y79-cell-line
#14
Rohini M Nair, Murali Ms Balla, Imran Khan, Ravi Kiran Reddy Kalathur, Paturu Kondaiah, Geeta K Vemuganti
BACKGROUND: Retinoblastoma (Rb), the most common childhood intraocular malignant tumor, is reported to have cancer stem cells (CSCs) similar to other tumors. Our previous investigation in primary tumors identified the small sized cells with low CD133 (Prominin-1) and high CD44 (Hyaluronic acid receptor) expression to be putative Rb CSCs using flow cytometry (FSClo /SSClo /CD133lo /CD44hi ). With this preliminary data, we have now utilized a comprehensive approach of in vitro characterization of Y79 Rb cell line following CSC enrichment using CD133 surface marker and subsequent validation to confirm the functional properties of CSCs...
November 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29110636/phenotypic-and-genotypic-aspects-of-townes-brock-syndrome-case-report-of-patient-in-southern-brazil-with-a-new-sall1-hotspot-region-nonsense-mutation
#15
Paulo Breno Noronha Liberalesso, Mara L Cordeiro, Simone Carreiro Vieira Karuta, Karyn Regina Jordão Koladicz, Anderson Nitsche, Bianca Simone Zeigelboim, Salmo Raskin, Michael Rauchman
BACKGROUND: Townes-Brocks syndrome (TBS) is a rare autosomal dominant condition characterized by renal, anal, limb, and auditory abnormalities. TBS diagnosis can be challenging in settings where genetic analysis is not readily available. TBS traits overlap with those of Goldenhar and VACTERL syndromes. CASE PRESENTATION: Here, we present the case of a 5-year-old Brazilian boy born with an anorectal abnormality, limb and external ears malformations, genitourinary anomalies, and a congenital heart defect...
November 6, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28760814/a-sall1-nurd-interaction-regulates-multipotent-nephron-progenitors-and-is-required-for-loop-of-henle-formation
#16
Jeannine M Basta, Lynn Robbins, Darcy R Denner, Grant R Kolar, Michael Rauchman
The formation of the proper number of nephrons requires a tightly regulated balance between renal progenitor cell self-renewal and differentiation. The molecular pathways that regulate the transition from renal progenitor to renal vesicle are not well understood. Here, we show that Sall1interacts with the nucleosome remodeling and deacetylase complex (NuRD) to inhibit premature differentiation of nephron progenitor cells. Disruption of Sall1-NuRD in vivo in knock-in mice (Δ SRM ) resulted in accelerated differentiation of nephron progenitors and bilateral renal hypoplasia...
September 1, 2017: Development
https://www.readbyqxmd.com/read/28759006/re-expression-of-sall1-in-podocytes-protects-against-adriamycin-induced-nephrosis
#17
Yoshiko Hosoe-Nagai, Teruo Hidaka, Ayano Sonoda, Yu Sasaki, Kanae Yamamoto-Nonaka, Takuto Seki, Rin Asao, Eriko Tanaka, Juan Alejandro Oliva Trejo, Fumiko Kodama, Miyuki Takagi, Nobuhiro Tada, Takashi Ueno, Ryuichi Nishinakamura, Yasuhiko Tomino, Katsuhiko Asanuma
The highly conserved spalt (sal) gene family members encode proteins characterized by multiple double zinc finger motifs of the C2H2 type. Humans and mice each have four known Sal-like genes (SALL1-4 in humans and Sall1-4 in mice). Sall1 is known to have a crucial role in kidney development. To explore the significance of Sall1 in differentiated podocytes, we investigated podocyte-specific Sall1-deficient mice (Sall1 KOp °d °/p °d °) using a podocin-Cre/loxP system and siRNA Sall1 knockdown (Sall1 KD) podocytes...
November 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28618409/identification-of-8-novel-mutations-in-nephrogenesis-related-genes-in-chinese-han-patients-with-unilateral-renal-agenesis
#18
Hangdi Wu, Qian Xu, Jingyuan Xie, Jun Ma, Panpan Qiao, Wen Zhang, Haijin Yu, Weiming Wang, Ying Qian, Qianying Zhang, Yiqing Guo, Yonghua Tang, Xiao-Nong Chen, Zhaohui Wang, Nan Chen
BACKGROUND: Few genetic studies have focused on unilateral renal agenesis (URA), which is a disorder with insidious clinical manifestations and a tendency to result in renal failure. We aimed to detect pathogenic mutations in nephrogenesis-related genes, which were identified by a literature review conducted among a large cohort of Chinese Han patients with URA. METHODS: Totally, 86 unrelated URA patients were included. All URA patients were diagnosed by employing radiological methods...
2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28459434/mice-deficient-in-nrros-show-abnormal-microglial-development-and-neurological-disorders
#19
Kit Wong, Rajkumar Noubade, Paolo Manzanillo, Naruhisa Ota, Oded Foreman, Jason A Hackney, Brad A Friedman, Rajita Pappu, Kimberly Scearce-Levie, Wenjun Ouyang
Microglia and other tissue-resident macrophages within the central nervous system (CNS) have essential roles in neural development, inflammation and homeostasis. However, the molecular pathways underlying their development and function remain poorly understood. Here we report that mice deficient in NRROS, a myeloid-expressed transmembrane protein in the endoplasmic reticulum, develop spontaneous neurological disorders. NRROS-deficient (Nrros(-/-)) mice show defects in motor functions and die before 6 months of age...
June 2017: Nature Immunology
https://www.readbyqxmd.com/read/28322736/sall1-and-sall4-repress-pou5f3-family-expression-to-allow-neural-patterning-differentiation-and-morphogenesis-in-xenopus-laevis
#20
Cameron R T Exner, Albert Y Kim, Sarah M Mardjuki, Richard M Harland
The embryonic precursor of the vertebrate central nervous system, the neural plate, is patterned along the anterior-posterior axis and shaped by morphogenetic movements early in development. We previously identified the genes sall1 and sall4, known regulators of pluripotency in other contexts, as transcriptional targets of developmental signaling pathways that regulate neural development. Here, we demonstrate that these two genes are required for induction of posterior neural fates, the cell shape changes that contribute to neural tube closure, and later neurogenesis...
May 1, 2017: Developmental Biology
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