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george q daley

Lara Wahlster, George Q Daley
De novo generation of haematopoietic stem cells from different human pluripotent stem cell sources remains a high priority for haematology and regenerative medicine. At present, efficient derivation of functional haematopoietic stem cells with the capability for definitive in vivo engraftment and multi-lineage potential remains challenging. Here, we discuss recent progress and strategies to overcome obstacles that have thwarted past efforts. In addition, we review promising advances in the generation of mature blood lineages and the potential of induced pluripotent stem cells...
October 10, 2016: Nature Cell Biology
Mauricio Cortes, Michael J Chen, David L Stachura, Sarah Y Liu, Wanda Kwan, Francis Wright, Linda T Vo, Lindsay N Theodore, Virginie Esain, Isaura M Frost, Thorsten M Schlaeger, Wolfram Goessling, George Q Daley, Trista E North
Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC) production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly reduced runx1 expression and Flk1(+)cMyb(+) HSPC numbers...
October 4, 2016: Cell Reports
R Grant Rowe, Leo D Wang, Silvia Coma, Areum Han, Ronald Mathieu, Daniel S Pearson, Samantha Ross, Patricia Sousa, Phi T Nguyen, Antony Rodriguez, Amy J Wagers, George Q Daley
For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood...
July 25, 2016: Journal of Experimental Medicine
John T Powers, Kaloyan M Tsanov, Daniel S Pearson, Frederik Roels, Catherine S Spina, Richard Ebright, Marc Seligson, Yvanka de Soysa, Patrick Cahan, Jessica Theißen, Ho-Chou Tu, Areum Han, Kyle C Kurek, Grace S LaPier, Jihan K Osborne, Samantha J Ross, Marcella Cesana, James J Collins, Frank Berthold, George Q Daley
Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B...
July 14, 2016: Nature
Jin Zhang, Sutheera Ratanasirintrawoot, Sriram Chandrasekaran, Zhaoting Wu, Scott B Ficarro, Chunxiao Yu, Christian A Ross, Davide Cacchiarelli, Qing Xia, Marc Seligson, Gen Shinoda, Wen Xie, Patrick Cahan, Longfei Wang, Shyh-Chang Ng, Supisara Tintara, Cole Trapnell, Tamer Onder, Yuin-Han Loh, Tarjei Mikkelsen, Piotr Sliz, Michael A Teitell, John M Asara, Jarrod A Marto, Hu Li, James J Collins, George Q Daley
The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs)...
July 7, 2016: Cell Stem Cell
Cheng-Xu Delon Toh, Jun-Wei Chan, Zheng-Shan Chong, Hao Fei Wang, Hong Chao Guo, Sandeep Satapathy, Dongrui Ma, Germaine Yen Lin Goh, Ekta Khattar, Lin Yang, Vinay Tergaonkar, Young-Tae Chang, James J Collins, George Q Daley, Keng Boon Wee, Chadi A El Farran, Hu Li, Yoon-Pin Lim, Frederic A Bard, Yuin-Han Loh
Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification...
June 21, 2016: Cell Reports
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
Jonathan Kimmelman, Insoo Hyun, Nissim Benvenisty, Timothy Caulfield, Helen E Heslop, Charles E Murry, Douglas Sipp, Lorenz Studer, Jeremy Sugarman, George Q Daley
No abstract text is available yet for this article.
May 19, 2016: Nature
George Q Daley, Insoo Hyun, Jane F Apperley, Roger A Barker, Nissim Benvenisty, Annelien L Bredenoord, Christopher K Breuer, Timothy Caulfield, Marcelle I Cedars, Joyce Frey-Vasconcells, Helen E Heslop, Ying Jin, Richard T Lee, Christopher McCabe, Megan Munsie, Charles E Murry, Steven Piantadosi, Mahendra Rao, Heather M Rooke, Douglas Sipp, Lorenz Studer, Jeremy Sugarman, Masayo Takahashi, Mark Zimmerman, Jonathan Kimmelman
The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research...
June 14, 2016: Stem Cell Reports
Jonathan Kimmelman, Helen E Heslop, Jeremy Sugarman, Lorenz Studer, Nissim Benvenisty, Timothy Caulfield, Insoo Hyun, Charles E Murry, Douglas Sipp, George Q Daley
No abstract text is available yet for this article.
May 14, 2016: Lancet
Timothy Caulfield, Douglas Sipp, Charles E Murry, George Q Daley, Jonathan Kimmelman
No abstract text is available yet for this article.
May 13, 2016: Science
Tariq I Mughal, Jerald P Radich, Michael W Deininger, Jane F Apperley, Timothy P Hughes, Christine J Harrison, Carlo Gambacorti-Passerini, Giuseppe Saglio, Jorge Cortes, George Q Daley
With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pathogenetic role in the development of chronic myeloid leukemia. This work was also of major importance to support the idea that cytogenetic changes were drivers of leukemogenesis. John Goldman originally made seminal contributions to the use of autologous and allogeneic stem cell transplantation from the late 1970s onwards...
May 2016: Haematologica
Peter Geon Kim, Matthew C Canver, Catherine Rhee, Samantha J Ross, June V Harriss, Ho-Chou Tu, Stuart H Orkin, Haley O Tucker, George Q Daley
In the developing mouse embryo, the first hematopoietic stem cells (HSCs) arise in the aorta-gonad-mesonephros (AGM) and mature as they transit through the fetal liver (FL). Compared with FL and adult HSCs, AGM HSCs have reduced repopulation potential in irradiated adult transplant recipients but mechanisms underlying this deficiency in AGM HSCs are poorly understood. By co-expression gene network analysis, we deduced that AGM HSCs show lower levels of interferon-α (IFN-α)/Jak-Stat1-associated gene expression than FL HSCs...
July 14, 2016: Blood
Christina Corre, Gen Shinoda, Hao Zhu, Diana L Cousminer, Christine Crossman, Christian Bellissimo, Anna Goldenberg, George Q Daley, Mark R Palmert
Growth and pubertal timing differ in boys and girls. Variants in/near LIN28B associate with age at menarche (AAM) in genome-wide association studies and some AAM-related variants associate with growth in a sex-specific manner. Sex-specific growth patterns in response to Lin28b perturbation have been detected in mice, and overexpression of Lin28a has been shown to alter pubertal timing in female mice. To investigate further how Lin28a and Lin28b affect growth and puberty in both males and females, we evaluated Lin28b loss-of-function (LOF) mice and Lin28a gain-of-function (GOF) mice...
March 2016: Journal of Endocrinology
Alejandro De Los Angeles, Francesco Ferrari, Ruibin Xi, Yuko Fujiwara, Nissim Benvenisty, Hongkui Deng, Konrad Hochedlinger, Rudolf Jaenisch, Soohyun Lee, Harry G Leitch, M William Lensch, Ernesto Lujan, Duanqing Pei, Janet Rossant, Marius Wernig, Peter J Park, George Q Daley
No abstract text is available yet for this article.
March 17, 2016: Nature
Alejandro De Los Angeles, Francesco Ferrari, Yuko Fujiwara, Ronald Mathieu, Soohyun Lee, Semin Lee, Ho-Chou Tu, Samantha Ross, Stephanie Chou, Minh Nguyen, Zhaoting Wu, Thorold W Theunissen, Benjamin E Powell, Sumeth Imsoonthornruksa, Jiekai Chen, Marti Borkent, Vladislav Krupalnik, Ernesto Lujan, Marius Wernig, Jacob H Hanna, Konrad Hochedlinger, Duanqing Pei, Rudolf Jaenisch, Hongkui Deng, Stuart H Orkin, Peter J Park, George Q Daley
No abstract text is available yet for this article.
March 17, 2016: Nature
Linwei Wu, Liem H Nguyen, Kejin Zhou, T Yvanka de Soysa, Lin Li, Jason B Miller, Jianmin Tian, Joseph Locker, Shuyuan Zhang, Gen Shinoda, Marc T Seligson, Lauren R Zeitels, Asha Acharya, Sam C Wang, Joshua T Mendell, Xiaoshun He, Jinsuke Nishino, Sean J Morrison, Daniel J Siegwart, George Q Daley, Ng Shyh-Chang, Hao Zhu
The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest let-7 overexpression abrogated MYC-driven liver cancer by antagonizing multiple let-7 sensitive oncogenes. However, the same level of overexpression blocked liver regeneration, while let-7 deletion enhanced it, demonstrating that distinct let-7 levels can mediate desirable phenotypes...
October 7, 2015: ELife
Heidi Anderson, Taylor C Patch, Pavankumar N G Reddy, Elliott J Hagedorn, Peter G Kim, Kathleen A Soltis, Michael J Chen, Owen J Tamplin, Maike Frye, Glenn A MacLean, Kathleen Hübner, Daniel E Bauer, John P Kanki, Guillaume Vogin, Nicholas C Huston, Minh Nguyen, Yuko Fujiwara, Barry H Paw, Dietmar Vestweber, Leonard I Zon, Stuart H Orkin, George Q Daley, Dhvanit I Shah
Rare endothelial cells in the aorta-gonad-mesonephros (AGM) transition into hematopoietic stem cells (HSCs) during embryonic development. Lineage tracing experiments indicate that HSCs emerge from cadherin 5 (Cdh5; vascular endothelial-cadherin)(+) endothelial precursors, and isolated populations of Cdh5(+) cells from mouse embryos and embryonic stem cells can be differentiated into hematopoietic cells. Cdh5 has also been widely implicated as a marker of AGM-derived hemogenic endothelial cells. Because Cdh5(-/-) mice embryos die before the first HSCs emerge, it is unknown whether Cdh5 has a direct role in HSC emergence...
December 24, 2015: Blood
Bin Xia Yang, Chadi A El Farran, Hong Chao Guo, Tao Yu, Hai Tong Fang, Hao Fei Wang, Sharon Schlesinger, Yu Fen Samantha Seah, Germaine Yen Lin Goh, Suat Peng Neo, Yinghui Li, Matthew C Lorincz, Vinay Tergaonkar, Tit-Meng Lim, Lingyi Chen, Jayantha Gunaratne, James J Collins, Stephen P Goff, George Q Daley, Hu Li, Frederic A Bard, Yuin-Han Loh
Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs...
September 24, 2015: Cell
Partha Pratim Das, David A Hendrix, Effie Apostolou, Alice H Buchner, Matthew C Canver, Semir Beyaz, Damir Ljuboja, Rachael Kuintzle, Woojin Kim, Rahul Karnik, Zhen Shao, Huafeng Xie, Jian Xu, Alejandro De Los Angeles, Yingying Zhang, Junho Choe, Don Leong Jia Jun, Xiaohua Shen, Richard I Gregory, George Q Daley, Alexander Meissner, Manolis Kellis, Konrad Hochedlinger, Jonghwan Kim, Stuart H Orkin
Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus...
September 1, 2015: Cell Reports
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