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Nature Biotechnology

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https://www.readbyqxmd.com/read/28504668/hla-e-expressing-pluripotent-stem-cells-escape-allogeneic-responses-and-lysis-by-nk-cells
#1
Germán G Gornalusse, Roli K Hirata, Sarah E Funk, Laura Riolobos, Vanda S Lopes, Gabriel Manske, Donna Prunkard, Aric G Colunga, Laïla-Aïcha Hanafi, Dennis O Clegg, Cameron Turtle, David W Russell
Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28504667/rapid-cloning-of-genes-in-hexaploid-wheat-using-cultivar-specific-long-range-chromosome-assembly
#2
Anupriya Kaur Thind, Thomas Wicker, Hana Šimková, Dario Fossati, Odile Moullet, Cécile Brabant, Jan Vrána, Jaroslav Doležel, Simon G Krattinger
Cereal crops such as wheat and maize have large repeat-rich genomes that make cloning of individual genes challenging. Moreover, gene order and gene sequences often differ substantially between cultivars of the same crop species. A major bottleneck for gene cloning in cereals is the generation of high-quality sequence information from a cultivar of interest. In order to accelerate gene cloning from any cropping line, we report 'targeted chromosome-based cloning via long-range assembly' (TACCA). TACCA combines lossless genome-complexity reduction via chromosome flow sorting with Chicago long-range linkage to assemble complex genomes...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28459452/targeting-genomic-rearrangements-in-tumor-cells-through-cas9-mediated-insertion-of-a-suicide-gene
#3
Zhang-Hui Chen, Yan P Yu, Ze-Hua Zuo, Joel B Nelson, George K Michalopoulos, Satdatshan Monga, Silvia Liu, George Tseng, Jian-Hua Luo
Specifically targeting genomic rearrangements and mutations in tumor cells remains an elusive goal in cancer therapy. Here, we used Cas9-based genome editing to introduce the gene encoding the prodrug-converting enzyme herpes simplex virus type 1 thymidine kinase (HSV1-tk) into the genomes of cancer cells carrying unique sequences resulting from genome rearrangements. Specifically, we targeted the breakpoints of TMEM135-CCDC67 and MAN2A1-FER fusions in human prostate cancer or hepatocellular carcinoma cells in vitro and in mouse xenografts...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28459451/generation-of-inner-ear-organoids-containing-functional-hair-cells-from-human-pluripotent-stem-cells
#4
Karl R Koehler, Jing Nie, Emma Longworth-Mills, Xiao-Ping Liu, Jiyoon Lee, Jeffrey R Holt, Eri Hashino
The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28459450/transplantation-of-engineered-organoids-enables-rapid-generation-of-metastatic-mouse-models-of-colorectal-cancer
#5
Kevin P O'Rourke, Evangelia Loizou, Geulah Livshits, Emma M Schatoff, Timour Baslan, Eusebio Manchado, Janelle Simon, Paul B Romesser, Benjamin Leach, Teng Han, Chantal Pauli, Himisha Beltran, Mark A Rubin, Lukas E Dow, Scott W Lowe
Colorectal cancer (CRC) is a leading cause of death in the developed world, yet facile preclinical models that mimic the natural stages of CRC progression are lacking. Through the orthotopic engraftment of colon organoids we describe a broadly usable immunocompetent CRC model that recapitulates the entire adenoma-adenocarcinoma-metastasis axis in vivo. The engraftment procedure takes less than 5 minutes, shows efficient tumor engraftment in two-thirds of mice, and can be achieved using organoids derived from genetically engineered mouse models (GEMMs), wild-type organoids engineered ex vivo, or from patient-derived human CRC organoids...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28459449/in-vivo-genome-editing-and-organoid-transplantation-models-of-colorectal-cancer-and-metastasis
#6
Jatin Roper, Tuomas Tammela, Naniye Malli Cetinbas, Adam Akkad, Ali Roghanian, Steffen Rickelt, Mohammad Almeqdadi, Katherine Wu, Matthias A Oberli, Francisco Sánchez-Rivera, Yoona K Park, Xu Liang, George Eng, Martin S Taylor, Roxana Azimi, Dmitriy Kedrin, Rachit Neupane, Semir Beyaz, Ewa T Sicinska, Yvelisse Suarez, James Yoo, Lillian Chen, Lawrence Zukerberg, Pekka Katajisto, Vikram Deshpande, Adam J Bass, Philip N Tsichlis, Jacqueline Lees, Robert Langer, Richard O Hynes, Jianzhu Chen, Arjun Bhutkar, Tyler Jacks, Ömer H Yilmaz
In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28459448/single-cell-topological-rna-seq-analysis-reveals-insights-into-cellular-differentiation-and-development
#7
Abbas H Rizvi, Pablo G Camara, Elena K Kandror, Thomas J Roberts, Ira Schieren, Tom Maniatis, Raul Rabadan
Transcriptional programs control cellular lineage commitment and differentiation during development. Understanding of cell fate has been advanced by studying single-cell RNA-sequencing (RNA-seq) but is limited by the assumptions of current analytic methods regarding the structure of data. We present single-cell topological data analysis (scTDA), an algorithm for topology-based computational analyses to study temporal, unbiased transcriptional regulation. Unlike other methods, scTDA is a nonlinear, model-independent, unsupervised statistical framework that can characterize transient cellular states...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28369033/crispr-cas9-epigenome-editing-enables-high-throughput-screening-for-functional-regulatory-elements-in-the-human-genome
#8
Tyler S Klann, Joshua B Black, Malathi Chellappan, Alexias Safi, Lingyun Song, Isaac B Hilton, Gregory E Crawford, Timothy E Reddy, Charles A Gersbach
Large genome-mapping consortia and thousands of genome-wide association studies have identified non-protein-coding elements in the genome as having a central role in various biological processes. However, decoding the functions of the millions of putative regulatory elements discovered in these studies remains challenging. CRISPR-Cas9-based epigenome editing technologies have enabled precise perturbation of the activity of specific regulatory elements. Here we describe CRISPR-Cas9-based epigenomic regulatory element screening (CERES) for improved high-throughput screening of regulatory element activity in the native genomic context...
April 3, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486470/erratum-an-optical-probe-of-synaptic-plasticity
#9
Tal Laviv, Ryohei Yasuda
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486469/digital-farming-attracts-cash-to-agtech-startups
#10
Emily Waltz
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486468/recent-patents-in-plant-organogenesis
#11
(no author information available yet)
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486467/academic-partnerships-2016
#12
Brady Huggett
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486466/erratum-drugging-the-gut-microbiome
#13
Ken Garber
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486465/fda-approves-parp-inhibitor-for-ovarian-cancer
#14
(no author information available yet)
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486464/discovering-and-linking-public-omics-data-sets-using-the-omics-discovery-index
#15
Yasset Perez-Riverol, Mingze Bai, Felipe da Veiga Leprevost, Silvano Squizzato, Young Mi Park, Kenneth Haug, Adam J Carroll, Dylan Spalding, Justin Paschall, Mingxun Wang, Noemi Del-Toro, Tobias Ternent, Peng Zhang, Nicola Buso, Nuno Bandeira, Eric W Deutsch, David S Campbell, Ronald C Beavis, Reza M Salek, Ugis Sarkans, Robert Petryszak, Maria Keays, Eoin Fahy, Manish Sud, Shankar Subramaniam, Ariana Barbera, Rafael C Jiménez, Alexey I Nesvizhskii, Susanna-Assunta Sansone, Christoph Steinbeck, Rodrigo Lopez, Juan A Vizcaíno, Peipei Ping, Henning Hermjakob
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486463/first-eczema-biologic-debuts-but-price-could-restrict-use
#16
Elie Dolgin
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486462/living-in-a-microbial-world
#17
Charles Schmidt
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486460/astex-shapes-cdk4-6-inhibitor-for-approval
#18
Mark Peplow
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486459/genentech-s-ocrevus-heralds-new-chapter-in-ms-treatment
#19
Cormac Sheridan
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28486458/first-quarter-biotech-job-picture
#20
Michael Francisco
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
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