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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...
March 18, 2017: Developmental Biology
Anne Buttgereit, Iva Lelios, Xueyang Yu, Melissa Vrohlings, Natalie R Krakoski, Emmanuel L Gautier, Ryuichi Nishinakamura, Burkhard Becher, Melanie Greter
No abstract text is available yet for this article.
January 19, 2017: Nature Immunology
Jing Dong, Annah Wyss, Jingyun Yang, T Ryan Price, Aude Nicolas, Michael Nalls, Greg Tranah, Nora Franceschini, Zongli Xu, Claudia Schulte, Alvaro Alonso, Steven R Cummings, Myriam Fornage, Dmitri Zaykin, Leping Li, Xuemei Huang, Stephen Kritchevsky, Yongmei Liu, Thomas Gasser, Robert S Wilson, Philip L De Jager, Andrew B Singleton, Jayant M Pinto, Tamara Harris, Thomas H Mosley, David A Bennett, Stephanie London, Lei Yu, Honglei Chen
The human sense of smell decreases with age, and a poor sense of smell are among the most important prodromal symptoms of several neurodegenerative diseases. Recent evidence further suggests a racial difference in the sense of smell among U.S. older adults. However, no genome-wide association study (GWAS) on the sense of smell has been conducted in African-Americans (AAs). We performed the first genome-wide meta-analysis of the sense of smell among 1979 AAs and 6582 European-Americans (EAs) from three U.S. aging cohorts...
November 23, 2016: Molecular Neurobiology
Anne Buttgereit, Iva Lelios, Xueyang Yu, Melissa Vrohlings, Natalie R Krakoski, Emmanuel L Gautier, Ryuichi Nishinakamura, Burkhard Becher, Melanie Greter
Microglia are the resident macrophages of the central nervous system (CNS). Gene expression profiling has identified Sall1, which encodes a transcriptional regulator, as a microglial signature gene. We found that Sall1 was expressed by microglia but not by other members of the mononuclear phagocyte system or by other CNS-resident cells. Using Sall1 for microglia-specific gene targeting, we found that the cytokine receptor CSF1R was involved in the maintenance of adult microglia and that the receptor for the cytokine TGF-β suppressed activation of microglia...
December 2016: Nature Immunology
Clara Lopes Novo, Peter J Rugg-Gunn
Pluripotent cells are characterized by a globally open and accessible chromatin organization that is thought to contribute to cellular plasticity and developmental decision-making. We recently identified the pluripotency factor Nanog as a key regulator of this form of chromatin architecture in mouse embryonic stem cells. In particular, we demonstrated that the transcription factors Nanog and Sall1 co-dependently mediate the epigenetic state of pericentromeric heterochromatin to reinforce a more open and accessible organization in pluripotent cells...
October 19, 2016: Nucleus
Raquel López-Mejías, Fernanda Genre, Sara Remuzgo-Martínez, Carlos González-Juanatey, Montserrat Robustillo-Villarino, Javier Llorca, Alfonso Corrales, Esther Vicente, José A Miranda-Filloy, César Magro, Beatriz Tejera-Segura, Marco A Ramírez Huaranga, Trinitario Pina, Ricardo Blanco, Juan J Alegre-Sancho, Enrique Raya, Verónica Mijares, Begoña Ubilla, María D Mínguez Sánchez, Carmen Gómez-Vaquero, Alejandro Balsa, Dora Pascual-Salcedo, Francisco J López-Longo, Patricia Carreira, Isidoro González-Álvaro, Luis Rodríguez-Rodríguez, Benjamín Fernández-Gutiérrez, Iván Ferraz-Amaro, Santos Castañeda, Javier Martín, Miguel A González-Gay
Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan...
August 18, 2016: Scientific Reports
Hideto Koso, Asano Tsuhako, Chen-Yi Lai, Yukihiro Baba, Makoto Otsu, Kazuko Ueno, Masao Nagasaki, Yutaka Suzuki, Sumiko Watanabe
Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte-derived macrophages into the CNS, resulting in the coexistence of these two populations within the same lesion, though their distinct features remain elusive. To investigate the impact of rod photoreceptor degeneration on microglial activation, we generated a toxin-mediated genetic model of rod degeneration. Rod injury induced microglial proliferation and migration toward the photoreceptors. Bone marrow transplantation revealed the invasion of monocyte-derived macrophages into the retina, with microglia and the infiltrating macrophages showing distinct distribution patterns in the retina...
November 2016: Glia
N Khayatzadeh, G Mészáros, Y T Utsunomiya, J F Garcia, U Schnyder, B Gredler, I Curik, J Sölkner
Identification of selection signatures is one of the current endeavors of evolutionary genetics. Admixed populations may be used to infer post-admixture selection. We calculated local ancestry for Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF), to infer such signals. Illumina Bovine SNP50 BeadChip data for 300 admixed, 88 SI and 97 RHF bulls were used. The average RHF ancestry across the whole genome was 0.70. To identify regions with high deviation from average, we considered two significance thresholds, based on a permutation test and extreme deviation from normal distribution...
December 2016: Animal Genetics
Tatsuya Sasaki, Yuka Tanaka, Kasem Kulkeaw, Ayako Yumine-Takai, Keai Sinn Tan, Ryuichi Nishinakamura, Junji Ishida, Akiyoshi Fukamizu, Daisuke Sugiyama
The aorta-gonad-mesonephros (AGM) region contains intra-aortic clusters (IACs) thought to have acquired hematopoietic stem cell (HSC) potential in vertebrate embryos. To assess extrinsic regulation of IACs in the AGM region, we employed mouse embryos harboring a Sall1-GFP reporter gene, which allows identification of mesonephros cells based on GFP expression. Analysis of AGM region tissue sections confirmed mesonephros GFP expression. Mesonephric cells sorted at E10.5 expressed mRNA encoding Csf1, a hematopoietic cytokine, and corresponding protein, based on real-time PCR and immunocytochemistry, respectively...
October 2016: Stem Cell Reviews
Clara Lopes Novo, Calvin Tang, Kashif Ahmed, Ugljesa Djuric, Eden Fussner, Nicholas P Mullin, Natasha P Morgan, Jasvinder Hayre, Arnold R Sienerth, Sarah Elderkin, Ryuichi Nishinakamura, Ian Chambers, James Ellis, David P Bazett-Jones, Peter J Rugg-Gunn
An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains...
May 1, 2016: Genes & Development
Fu-Jun Lin, Wei Lu, Daniel Gale, Yao Yao, Ren Zou, Fan Bian, Geng-Ru Jiang
Townes-Brocks syndrome (TBS) is a rare autosomal dominant congenital anomaly syndrome characterized by the triad of anorectal, hand and external ear malformations. Kidney involvement is less common and may progress to end-stage renal failure (ESRF) early in life. The present study reports the case of a male patient presenting with multiple bilateral cortical kidney cysts at the age of 4 years, at which time the kidneys were of normal size and function. A clinical diagnosis of autosomal recessive polycystic kidney disease was made initially as the patient's parents are clinically healthy...
April 2016: Experimental and Therapeutic Medicine
Se Eun Kim, Ji Woo Kim, Yeong Ji Kim, Deug-Nam Kwon, Jin-Hoi Kim, Man-Jong Kang
The Sal-like 1 gene (Sall1) is essential for kidney development, and mutations in this gene result in abnormalities in the kidneys. Mice lacking Sall1 show agenesis or severe dysgenesis of the kidneys. In a recent study, blastocyst complementation was used to develop mice and pigs with exogenic organs. In the present study, transcription activator-like effector nuclease (TALEN)-mediated homologous recombination was used to produce Sall1-knockout porcine fibroblasts for developing knockout pigs. The vector targeting the Sall1 locus included a 5...
April 2016: Asian-Australasian Journal of Animal Sciences
Yuika Morita, Peter Andersen, Akitsu Hotta, Yuko Tsukahara, Noriko Sasagawa, Naoko Hayashida, Chizuko Koga, Misato Nishikawa, Yumiko Saga, Sylvia M Evans, Kazuko Koshiba-Takeuchi, Ryuichi Nishinakamura, Yoshinori Yoshida, Chulan Kwon, Jun K Takeuchi
Cardiac progenitor cells (CPCs) are a crucial source of cells in cardiac development and regeneration. However, reported CPCs are heterogeneous, and no gene has been identified to transiently mark undifferentiated CPCs throughout heart development. Here we show that Spalt-like gene 1 (Sall1), a zing-finger transcription factor, is expressed in undifferentiated CPCs giving rise to both left and right ventricles. Sall1 was transiently expressed in precardiac mesoderm contributing to the first heart field (left ventricle precursors) but not in the field itself...
March 2016: Journal of Molecular and Cellular Cardiology
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
Ryuji Morizane, Albert Q Lam, Benjamin S Freedman, Seiji Kishi, M Todd Valerius, Joseph V Bonventre
Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) may enable organ regeneration, disease modeling and drug screening. We report an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+ SALL1+ WT1+ PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+ LHX1+ renal vesicles that self-organize into nephron structures...
November 2015: Nature Biotechnology
Shunsuke Tanigawa, Nirmala Sharma, Michael D Hall, Ryuichi Nishinakamura, Alan O Perantoni
Understanding the mechanisms responsible for nephrogenic stem cell preservation and commitment is fundamental to harnessing the potential of the metanephric mesenchyme (MM) for nephron regeneration. Accordingly, we established a culture model that preferentially expands the MM SIX2+ progenitor pool using leukemia inhibitory factor (LIF), a Rho kinase inhibitor (ROCKi), and extracellular matrix. Passaged MM cells express the key stem cell regulators Six2 and Pax2 and remain competent to respond to WNT4 induction and form mature tubular epithelia and glomeruli...
September 8, 2015: Stem Cell Reports
Sara Hirsch, Tarek El-Achkar, Lynn Robbins, Jeannine Basta, Monique Heitmeier, Ryuichi Nishinakamura, Michael Rauchman
It has been postulated that developmental pathways are reutilized during repair and regeneration after injury, but functional analysis of many genes required for kidney formation has not been performed in the adult organ. Mutations in SALL1 cause Townes-Brocks syndrome (TBS) and nonsyndromic congenital anomalies of the kidney and urinary tract, both of which lead to childhood kidney failure. Sall1 is a transcriptional regulator that is expressed in renal progenitor cells and developing nephrons in the embryo...
November 15, 2015: American Journal of Physiology. Renal Physiology
Anthony Atala
No abstract text is available yet for this article.
August 2015: Journal of Urology
Lihua Dong, Stefan Pietsch, Christoph Englert
Mutations in Wilms' tumor 1 (WT1) cause a wide spectrum of renal manifestations, eventually leading to end-stage kidney failure. Insufficient understanding of WT1's molecular functions in kidney development has hampered efficient therapeutic applications for WT1-associated diseases. Recently, the generation and characterization of mouse models and application of multiple state-of-the-art approaches have significantly expanded our understanding of the molecular mechanisms of how WT1 mutations lead to kidney failure...
October 2015: Kidney International
Chunlong Zhang, Hongyan Zhao, Jie Li, Hongbo Liu, Fang Wang, Yanjun Wei, Jianzhong Su, Dongwei Zhang, Tiefu Liu, Yan Zhang
Abnormal DNA methylation is known as playing an important role in the tumorgenesis. It is helpful for distinguishing the specificity of diagnosis and therapeutic targets for cancers based on characteristics of DNA methylation patterns across cancers. High throughput DNA methylation analysis provides the possibility to comprehensively filter the epigenetics diversity across various cancers. We integrated whole-genome methylation data detected in 798 samples from seven cancers. The hierarchical clustering revealed the existence of cancer-specific methylation pattern...
2015: PloS One
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