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george q daley

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https://www.readbyqxmd.com/read/28619647/using-crispr-cas9-to-generate-gene-corrected-autologous-ipscs-for-the-treatment-of-inherited-retinal-degeneration
#1
Erin R Burnight, Manav Gupta, Luke A Wiley, Kristin R Anfinson, Audrey Tran, Robinson Triboulet, Jeremy M Hoffmann, Darcey L Klaahsen, Jeaneen L Andorf, Chunhua Jiao, Elliott H Sohn, Malavika K Adur, Jason W Ross, Robert F Mullins, George Q Daley, Thorsten M Schlaeger, Edwin M Stone, Budd A Tucker
Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function...
June 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28514439/haematopoietic-stem-and-progenitor-cells-from-human-pluripotent-stem-cells
#2
Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A Goettel, Erik Serrao, R Grant Rowe, Mohan Malleshaiah, Irene Wong, Patricia Sousa, Ted N Zhu, Andrea Ditadi, Gordon Keller, Alan N Engelman, Scott B Snapper, Sergei Doulatov, George Q Daley
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28429768/reassembling-embryos-in-vitro-from-component-stem-cells
#3
Caroline Kubaczka, George Q Daley
Researchers at the University of Cambridge, UK have succeeded in reconstructing mouse embryos by combining pluripotent embryonic and multipotent trophoblast stem cells in a 3D scaffold; the study from the laboratory of Professor Zernicka-Goetz, recently published in Science, provides a break-through tool to probe early mammalian development outside the uterus. Achieving a similar feat with human cells might necessitate reconsideration of the 14-day rule as a limitation of such research.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28350984/autophagy-it-s-in-your-blood
#4
Sergei Doulatov, George Q Daley
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28296612/polar-extremes-in-the-clinical-use-of-stem-cells
#5
George Q Daley
The U.S. biotechnology and pharmaceutical industries arguably lead the world in innovation while operating under stringent regulations set by the Food and Drug Administration (FDA). Although flexible pathways exist to accelerate the development or approval of treatments for serious illnesses or..
March 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28272977/signaling-through-rna-binding-proteins-as-a-cell-fate-regulatory-mechanism
#6
Kaloyan M Tsanov, George Q Daley
No abstract text is available yet for this article.
April 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28179501/drug-discovery-for-diamond-blackfan-anemia-using-reprogrammed-hematopoietic-progenitors
#7
Sergei Doulatov, Linda T Vo, Elizabeth R Macari, Lara Wahlster, Melissa A Kinney, Alison M Taylor, Jessica Barragan, Manav Gupta, Katherine McGrath, Hsiang-Ying Lee, Jessica M Humphries, Alex DeVine, Anupama Narla, Blanche P Alter, Alan H Beggs, Suneet Agarwal, Benjamin L Ebert, Hanna T Gazda, Harvey F Lodish, Colin A Sieff, Thorsten M Schlaeger, Leonard I Zon, George Q Daley
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077678/disruptive-reproductive-technologies
#8
REVIEW
I Glenn Cohen, George Q Daley, Eli Y Adashi
In vitro gametogenesis raises new possibilities for reproductive and regenerative medicine as well as vexing policy challenges.
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28009288/engineered-murine-hscs-reconstitute-multi-lineage-hematopoiesis-and-adaptive-immunity
#9
Yi-Fen Lu, Patrick Cahan, Samantha Ross, Julie Sahalie, Patricia M Sousa, Brandon K Hadland, Wenqing Cai, Erik Serrao, Alan N Engelman, Irwin D Bernstein, George Q Daley
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27992407/lin28-phosphorylation-by-mapk-erk-couples-signalling-to-the-post-transcriptional-control-of%C3%A2-pluripotency
#10
Kaloyan M Tsanov, Daniel S Pearson, Zhaoting Wu, Areum Han, Robinson Triboulet, Marc T Seligson, John T Powers, Jihan K Osborne, Susan Kane, Steven P Gygi, Richard I Gregory, George Q Daley
Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27974805/stem-cells-valine-starvation-leads-to-a-hungry-niche
#11
COMMENT
R Grant Rowe, George Q Daley
No abstract text is available yet for this article.
January 12, 2017: Nature
https://www.readbyqxmd.com/read/27777239/tgf-%C3%AE-inhibitors-stimulate-red-blood-cell-production-by-enhancing-self-renewal-of-bfu-e-erythroid-progenitors
#12
Xiaofei Gao, Hsiang-Ying Lee, Edroaldo Lummertz da Rocha, Cheng Zhang, Yi-Fen Lu, Dandan Li, Yuxiong Feng, Jideofor Ezike, Russell R Elmes, M Inmaculada Barrasa, Patrick Cahan, Hu Li, George Q Daley, Harvey F Lodish
Burst-forming unit erythroid progenitors (BFU-Es) are so named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of "bursts" of smaller erythroid colonies derived from the later colony-forming unit erythroid progenitor erythropoietin (Epo)-dependent progenitors. "Early" BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do "late" BFU-Es forming small colonies, but the mechanism underlying this heterogeneity remains unknown...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27723718/progress-towards-generation-of-human-haematopoietic-stem-cells
#13
REVIEW
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...
November 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27705794/developmental-vitamin-d-availability-impacts-hematopoietic-stem-cell-production
#14
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
https://www.readbyqxmd.com/read/27401346/developmental-regulation-of-myeloerythroid-progenitor-function-by-the-lin28b-let-7-hmga2-axis
#15
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
https://www.readbyqxmd.com/read/27383785/multiple-mechanisms-disrupt-the-let-7-microrna-family-in-neuroblastoma
#16
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
https://www.readbyqxmd.com/read/27320042/lin28-regulates-stem-cell-metabolism-and-conversion-to-primed-pluripotency
#17
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
https://www.readbyqxmd.com/read/27292646/rnai-reveals-phase-specific-global-regulators-of-human-somatic-cell-reprogramming
#18
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
https://www.readbyqxmd.com/read/27257760/engineering-hematopoietic-stem-cells-lessons-from-development
#19
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/27193661/policy-global-standards-for-stem-cell-research
#20
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
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