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https://www.readbyqxmd.com/read/28462385/serotonin-activated-hepatic-stellate-cells-contribute-to-sex-disparity-in-hepatocellular-carcinoma
#1
Qiqi Yang, Chuan Yan, Chunyue Yin, Zhiyuan Gong
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) occurs more frequently and aggressively in men than in women. Although sex hormones are believed to play a critical role in this disparity, the possible contribution of other factors largely is unknown. We aimed to investigate the role of serotonin on its contribution of sex discrepancy during HCC. METHODS: By using an inducible zebrafish HCC model through hepatocyte-specific transgenic kras(V12) expression, differential rates of HCC in male and female fish were characterized by both pharmaceutical and genetic interventions...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28440736/levistilide-a-inhibits-angiogenesis-in-liver-fibrosis-via-vascular-endothelial-growth-factor-signaling-pathway
#2
Zhi-Min Zhao, Hong-Liang Liu, Xin Sun, Tao Guo, Li Shen, Yan-Yan Tao, Cheng-Hai Liu
Levistilide A (C24H28O4, molecular weight = 380.48) derived from Angelica sinensis (Danggui) has been reported to inhibit hepatic stellate cell proliferation. This study investigated the effects of levistilide A on liver fibrosis relating to angiogenesis, particularly on the characteristic change in liver sinusoidal endothelial cells. LX-2 cells were activated by TGF-β1, and the human hepatic sinusoidal endothelial cells (HHSECs) were induced by endothelial cell growth supplement. Cell viability was detected using a methylthiazoldiphenyl-tetrazolium bromide assay; F-actin was visualized through the fluorescence probe method; cell proliferation was examined using the EdU kit; antiangiogenesis activity was assessed using the tube formation assay and transgenic zebrafish model...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28394883/pdgf-signalling-guides-neural-crest-contribution-to-the-haematopoietic-stem-cell-specification-niche
#3
Erich W Damm, Wilson K Clements
Haematopoietic stem cells (HSCs) support maintenance of the haematopoietic and immune systems throughout the life of vertebrates, and are the therapeutic component of bone marrow transplants. Understanding native specification of HSCs, to uncover key signals that might help improve in vitro directed differentiation protocols, has been a long-standing biomedical goal. The current impossibility of specifying true HSCs in vitro suggests that key signals remain unknown. We speculated that such signals might be presented by surrounding 'niche' cells, but no such cells have been defined...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28170201/concise-review-hematopoietic-stem-cell-origins-lessons-from-embryogenesis-for-improving-regenerative-medicine
#4
Adriana De La Garza, Arpan Sinha, Teresa V Bowman
Hematopoietic stem cells (HSCs) have extensive regenerative capacity to replace all blood cell types, an ability that is harnessed in the clinic for bone marrow transplantation. Finding appropriate donors remains a major limitation to more extensive usage of HSC-based therapies. Derivation of patient-specific HSCs from pluripotent stem cells offers great promise to remedy this problem if scientists could crack the code on how to make robust, transplantable HSCs in a dish. Studies delving into the native origins of HSC production during embryonic development should supply the necessary playbook...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28129843/hematopoietic-stem-cell-development-using-the-zebrafish-to-identify-extrinsic-and-intrinsic-mechanisms-regulating-hematopoiesis
#5
J M Frame, S-E Lim, T E North
Hematopoietic stem cells (HSCs) reside at the apex of the hematopoietic hierarchy, giving rise to each of the blood lineages found throughout the lifetime of the organism. Since the genetic programs regulating HSC development are highly conserved between vertebrate species, experimental studies in zebrafish have not only complemented observations reported in mammals but have also yielded important discoveries that continue to influence our understanding of HSC biology and homeostasis. Here, we summarize findings that have established zebrafish as an important conserved model for the study of hematopoiesis, and describe methods that can be utilized for future investigations of zebrafish HSC biology...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28008181/haematopoietic-stem-cells-show-their-true-colours
#6
Trista E North, Wolfram Goessling
Delineating the behaviour of haematopoietic stem cells (HSCs) in vivo has thus far proven challenging. Two studies in zebrafish and mouse models now track HSCs in vivo using fate mapping with multicolour approaches to provide further insights into clonal events that regulate blood development, HSC function and differentiation during homeostasis and stress conditions.
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27958775/distinct-molecular-signature-of-murine-fetal-liver-and-adult-hematopoietic-stem-cells-identify-novel-regulators-of-hematopoietic-stem-cell-function
#7
Javed K Manesia, Monica Franch, Daniel Tabas-Madrid, Ruben Nogales-Cadenas, Thomas Vanwelden, Elisa Van Den Bosch, Zhuofei Xu, Alberto Pascual-Montano, Satish Khurana, Catherine M Verfaillie
During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs...
April 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27870830/clonal-fate-mapping-quantifies-the-number-of%C3%A2-haematopoietic-stem-cells-that-arise-during%C3%A2-development
#8
Jonathan Henninger, Buyung Santoso, Stefan Hans, Ellen Durand, Jessica Moore, Christian Mosimann, Michael Brand, David Traver, Leonard Zon
Haematopoietic stem cells (HSCs) arise in the developing aorta during embryogenesis. The number of HSC clones born has been estimated through transplantation, but experimental approaches to assess the absolute number of forming HSCs in a native setting have remained challenging. Here, we applied single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs. Targeting creER(T2) in developing cd41:eGFP(+) HSCs enabled long-term assessment of their blood contribution. We also applied the Brainbow-based multicolour Zebrabow system with drl:creER(T2) that is active in early haematopoiesis to induce heritable colour barcoding unique to each HSC and its progeny...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27861498/somite-derived-retinoic-acid-regulates-zebrafish-hematopoietic-stem-cell-formation
#9
Laura M Pillay, Kacey J Mackowetzky, Sonya A Widen, Andrew Jan Waskiewicz
Hematopoietic stem cells (HSCs) are multipotent progenitors that generate all vertebrate adult blood lineages. Recent analyses have highlighted the importance of somite-derived signaling factors in regulating HSC specification and emergence from dorsal aorta hemogenic endothelium. However, these factors remain largely uncharacterized. We provide evidence that the vitamin A derivative retinoic acid (RA) functions as an essential regulator of zebrafish HSC formation. Temporal analyses indicate that RA is required for HSC gene expression prior to dorsal aorta formation, at a time when the predominant RA synthesis enzyme, aldh1a2, is strongly expressed within the paraxial mesoderm and somites...
2016: PloS One
https://www.readbyqxmd.com/read/27751705/cebp%C3%AE-is-essential-for-the-embryonic-myeloid-progenitor-and-neutrophil-maintenance-in-zebrafish
#10
Yimei Dai, Lu Zhu, Zhibin Huang, Minyu Zhou, Wan Jin, Wei Liu, Mengchang Xu, Tao Yu, Yiyue Zhang, Zilong Wen, Wangjun Liao, Wenqing Zhang
In vertebrates, myeloid cells arise from multiple waves of development: the first or embryonic wave of myelopoiesis initiates early from non-hematopoietic stem cell (HSC) precursors and gives rise to myeloid cells transiently during early development; whereas the second or adult wave of myelopoiesis emerges later from HSCs and produces myeloid cells continually during fetal and adult life. In the past decades, a great deal has been learnt about the development of myeloid cells from adult myelopoiesis, yet the genetic network governing embryonic myelopoiesis remains poorly defined...
September 3, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/27638855/evi1-regulates-notch-activation-to-induce-zebrafish-hematopoietic-stem-cell-emergence
#11
Martina Konantz, Elisa Alghisi, Joëlle S Müller, Anna Lenard, Virginie Esain, Kelli J Carroll, Lothar Kanz, Trista E North, Claudia Lengerke
During development, hematopoietic stem cells (HSCs) emerge from aortic endothelial cells (ECs) through an intermediate stage called hemogenic endothelium by a process known as endothelial-to-hematopoietic transition (EHT). While Notch signaling, including its upstream regulator Vegf, is known to regulate this process, the precise molecular control and temporal specificity of Notch activity remain unclear. Here, we identify the zebrafish transcriptional regulator evi1 as critically required for Notch-mediated EHT In vivo live imaging studies indicate that evi1 suppression impairs EC progression to hematopoietic fate and therefore HSC emergence...
November 2, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27520065/rna-polymerase-ii-pausing-modulates-hematopoietic-stem-cell-emergence-in-zebrafish
#12
Qiwen Yang, Xiuli Liu, Ting Zhou, Jennifer Cook, Kim Nguyen, Xiaoying Bai
The promoter-proximal pausing of RNA polymerase II (Pol II) plays a critical role in regulating metazoan gene transcription. Despite the prevalence of Pol II pausing across the metazoan genomes, little is known about the in vivo effect of Pol II pausing on vertebrate development. We use the emergence of hematopoietic stem cells (HSCs) in zebrafish embryos as a model to investigate the role of Pol II pausing in vertebrate organogenesis. Disrupting Pol II pausing machinery causes a severe reduction of HSC specification, a defect that can be effectively rescued by inhibiting Pol II elongation...
September 29, 2016: Blood
https://www.readbyqxmd.com/read/27484862/concise-review-hematopoietic-stem-cell-origins-lessons-from-embryogenesis-for-improving-regenerative-medicine
#13
Adriana De La Garza, Arpan Sinha, Teresa V Bowman
: Hematopoietic stem cells (HSCs) have extensive regenerative capacity to replace all blood cell types, an ability that is harnessed in the clinic for bone marrow transplantation. Finding appropriate donors remains a major limitation to more extensive usage of HSC-based therapies. Derivation of patient-specific HSCs from pluripotent stem cells offers great promise to remedy this problem if scientists could crack the code on how to make robust, transplantable HSCs in a dish. Studies delving into the native origins of HSC production during embryonic development should supply the necessary playbook...
August 2, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27443939/epigenetic-regulation-of-hematopoietic-stem-cell-development
#14
C Li, T Evans, M G Goll
Hematopoietic stem cells (HSCs) are multipotent self-renewing precursors with the capacity to differentiate into all adult blood cell lineages. HSC development is a highly orchestrated process regulated by multiple transcription factors and signaling pathways. Emerging evidence suggests that epigenetic regulation is an additional essential component of HSC development. Powerful genetic and imaging approaches, combined with conservation of mammalian programs, have made zebrafish a prominent model for the study of HSC production...
2016: Methods in Cell Biology
https://www.readbyqxmd.com/read/27434411/targeting-ddr2-in-head-and-neck-squamous-cell-carcinoma-with-dasatinib
#15
Anne von Mässenhausen, Christine Sanders, Johannes Brägelmann, Martina Konantz, Angela Queisser, Wenzel Vogel, Glen Kristiansen, Stefan Duensing, Andreas Schröck, Friedrich Bootz, Peter Brossart, Jutta Kirfel, Claudia Lengerke, Sven Perner
Squamous cell carcinoma of the head and neck (HNSCC) is the tenth most common tumor entity in men worldwide. Nevertheless therapeutic options are mostly limited to surgery and radio-chemotherapy resulting in 5-year survival rates of around 50%. Therefore new therapeutic options are urgently needed. During the last years, targeting of receptor tyrosine kinases has emerged as a promising strategy that can complement standard therapeutical approaches. Here, we aimed at investigating if the receptor tyrosine kinase DDR2 is a targetable structure in HNSCC...
November 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27402973/tfec-controls-the-hematopoietic-stem-cell-vascular-niche-during-zebrafish-embryogenesis
#16
Christopher B Mahony, Richard J Fish, Corentin Pasche, Julien Y Bertrand
In mammals, embryonic hematopoiesis occurs in successive waves, culminating with the emergence of hematopoietic stem cells (HSCs) in the aorta. HSCs first migrate to the fetal liver (FL), where they expand, before they seed the bone marrow niche, where they will sustain hematopoiesis throughout adulthood. In zebrafish, HSCs emerge from the dorsal aorta and colonize the caudal hematopoietic tissue (CHT). Recent studies showed that they interact with endothelial cells (ECs), where they expand, before they reach their ultimate niche, the kidney marrow...
September 8, 2016: Blood
https://www.readbyqxmd.com/read/27257760/engineering-hematopoietic-stem-cells-lessons-from-development
#17
REVIEW
R Grant Rowe, Joseph Mandelbaum, Leonard I Zon, George Q Daley
Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs...
June 2, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27197559/cyp2aa9-regulates-haematopoietic-stem-cell-development-in-zebrafish
#18
Jingying Chen, Jianbo He, Li Li, Deqin Yang, Lingfei Luo
Definitive haematopoiesis occurs during the lifetime of an individual, which continuously replenishes all blood and immune cells. During embryonic development, haematopoietic stem cell (HSC) formation is tightly controlled by growth factors, signalling molecules and transcription factors. But little is known about roles of the cytochrome P450 (CYP) 2 family member in the haematopoiesis. Here we report characterization and functional studies of Cyp2aa9, a novel zebrafish Cyp2 family member. And demonstrate that the cyp2aa9 is required for the HSC formation and homeostasis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27015586/endothelial-to-hematopoietic-transition-notch-ing-vessels-into-blood
#19
Dirk Kanz, Martina Konantz, Elisa Alghisi, Trista E North, Claudia Lengerke
During development, hematopoietic stem cells (HSCs) are formed in a temporally and spatially restricted manner, arising from specialized endothelial cells (ECs) in the ventral wall of the dorsal aorta within the evolutionary conserved aorta-gonad-mesonephros region. Our understanding of the processes regulating the birth of HSCs from ECs has been recently advanced by comprehensive molecular analyses of developing murine hematopoietic cell populations complemented by studies in the zebrafish model, with the latter offering unique advantages for genetic studies and direct in vivo visualization of HSC emergence...
April 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/26905203/gata-factor-g-protein-coupled-receptor-circuit-suppresses-hematopoiesis
#20
Xin Gao, Tongyu Wu, Kirby D Johnson, Jamie L Lahvic, Erik A Ranheim, Leonard I Zon, Emery H Bresnick
Hematopoietic stem cells (HSCs) originate from hemogenic endothelium within the aorta-gonad-mesonephros (AGM) region of the mammalian embryo. The relationship between genetic circuits controlling stem cell genesis and multi-potency is not understood. A Gata2 cis element (+9.5) enhances Gata2 expression in the AGM and induces the endothelial to HSC transition. We demonstrated that GATA-2 rescued hematopoiesis in +9.5(-/-) AGMs. As G-protein-coupled receptors (GPCRs) are the most common targets for FDA-approved drugs, we analyzed the GPCR gene ensemble to identify GATA-2-regulated GPCRs...
March 8, 2016: Stem Cell Reports
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