2018年11月15日星期四

Abbkine Top Selling Products for Immunology

Abbkine focuses on Immunology and Cytology. Here, we present our top selling products in immunology research, from basic Immunology products such as Protein Extraction and Quantification kits to Tag Antibodies, Primary Antibodies and Secondary Antibodies, to help your research career.

[pdfjs-viewer url="https%3A%2F%2Fwww.abbkine.com%2Fwp-content%2Fuploads%2F2018%2F11%2FAbbkine-Top-Selling-Products-for-Immunology.pdf" viewer_width=100% viewer_height=1360px fullscreen=true download=true print=true]

Abbkine Top Selling Products for Immunology

Abbkine focuses on Immunology and Cytology. Here, we present our top selling products in immunology research, from basic Immunology products such as Protein Extraction and Quantification kits to Tag Antibodies, Primary Antibodies and Secondary Antibodies, to help your research career.

[pdfjs-viewer url="https%3A%2F%2Fwww.abbkine.com%2Fwp-content%2Fuploads%2F2018%2F11%2FAbbkine-Top-Selling-Products-for-Immunology.pdf" viewer_width=100% viewer_height=1360px fullscreen=true download=true print=true]

Abbkine Top Selling Products for Cytology

Abbkine focuses on Proteomics and Cytology. Here, we present our top selling products in cytology research, from dyes and kits for cell status detection, organelle extraction kits, cell substructure staining and cell metabolism detection products, to cytokine for cell culture and protein detection kits, to help your research career.

[pdfjs-viewer url="https%3A%2F%2Fwww.abbkine.com%2Fwp-content%2Fuploads%2F2018%2F11%2FAbbkine-Top-Selling-Products-for-Cytology.pdf" viewer_width=100% viewer_height=1360px fullscreen=true download=true print=true]

Abbkine Top Selling Products for Cytology

Abbkine focuses on Proteomics and Cytology. Here, we present our top selling products in cytology research, from dyes and kits for cell status detection, organelle extraction kits, cell substructure staining and cell metabolism detection products, to cytokine for cell culture and protein detection kits, to help your research career.

[pdfjs-viewer url="https%3A%2F%2Fwww.abbkine.com%2Fwp-content%2Fuploads%2F2018%2F11%2FAbbkine-Top-Selling-Products-for-Cytology.pdf" viewer_width=100% viewer_height=1360px fullscreen=true download=true print=true]

Cyclosporine H Overcomes Innate Immune Restrictions to Improve Lentiviral Transduction and Gene Editing In Human Hematopoietic Stem Cells

Content introduction:

  • Cyclosporine H Overcomes Innate Immune Restrictions to Improve Lentiviral Transduction and Gene Editing In Human Hematopoietic Stem Cells

  • Notch-Induced miR-708 Antagonizes Satellite Cell Migration and Maintains Quiescence

  • In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity

  • A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

  • Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions


1. Cyclosporine H Overcomes Innate Immune Restrictions to Improve Lentiviral Transduction and Gene Editing In Human Hematopoietic Stem Cells

Innate immune factors may restrict hematopoietic stem cell (HSC) genetic engineering and contribute to broad individual variability in gene therapy outcomes. Here, Carolina Petrillo at IRCCS San Raffaele Scientific Institute in Milan, Italy and his colleagues show that HSCs harbor an early, constitutively active innate immune block to lentiviral transduction that can be efficiently overcome by cyclosporine H (CsH). CsH potently enhances gene transfer and editing in human long-term repopulating HSCs by inhibiting interferon-induced transmembrane protein 3 (IFITM3), which potently restricts VSV glycoprotein-mediated vector entry. Importantly, individual variability in endogenous IFITM3 levels correlated with permissiveness of HSCs to lentiviral transduction, suggesting that CsH treatment will be useful for improving ex vivo gene therapy and standardizing HSC transduction across patients. Overall, their work unravels the involvement of innate pathogen recognition molecules in immune blocks to gene correction in primary human HSCs and highlights how these roadblocks can be overcome to develop innovative cell and gene therapies.



Read more, please click https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30489-2

2. Notch-Induced miR-708 Antagonizes Satellite Cell Migration and Maintains Quiescence

Critical features of stem cells include anchoring within a niche and activation upon injury. Notch signaling maintains skeletal muscle satellite (stem) cell quiescence by inhibiting differentiation and inducing expression of extracellular components of the niche. However, the complete spectrum of how Notch safeguards quiescence is not well understood. Here, Meryem B. Baghdadi at Institut Pasteur in Paris, France and his colleagues perform Notch ChIP-sequencing and small RNA sequencing in satellite cells and identify the Notch-induced microRNA-708, which is a mirtron that is highly expressed in quiescent cells and sharply downregulated in activated cells. They employ in vivo and ex vivo functional studies, in addition to live imaging, to show that miR-708 regulates quiescence and self-renewal by antagonizing cell migration through targeting the transcripts of the focal-adhesion-associated protein Tensin3. Therefore, this study identifies a Notch-miR708-Tensin3 axis and suggests that Notch signaling can regulate satellite cell quiescence and transition to the activation state through dynamic regulation of the migratory machinery.

Read more, please click https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30481-8

3. In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity

Transplantation of human hepatocytes (HHs) holds significant potential for treating liver diseases. However, the supply of transplantable HHs is severely constrained by limited donor availability and compromised capacity for in vitro expansion. In response to chronic injury, some HHs are reprogrammed into proliferative cells that express both hepatocyte and progenitor markers, suggesting exploitable strategies for expanding HHs in vitro. Here, Kun Zhang at Tongji University School of Medicine in Shanghai, China and his colleagues report defined medium conditions that allow 10,000-fold expansion of HHs. These proliferating HHs are bi-phenotypic, partially retaining hepatic features while gaining expression of progenitor-associated genes. Importantly, these cells engraft into injured mouse liver at a level comparable to primary HHs, and they undergo maturation following transplantation in vivo or differentiation in vitro. Thus, this study provides a protocol that enables large-scale expansion of transplantable HHs, which could be further developed for modeling and treating human liver disease.

Read more, please click https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30499-5

4. A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, Helen H.N. Yan at The University of Hong Kong in Pokfulam, Hong Kong and his colleagues have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.

Read more, please click https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30480-6

5. Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions

Unisexual reproduction is widespread among lower vertebrates, but not in mammals. Deletion of the H19 imprinted region in immature oocytes produced bimaternal mice with defective growth; however, bipaternal reproduction has not been previously achieved in mammals. Zhi-Kun Li at Institute of Zoology, Chinese Academy of Sciences in Beijing, China and his colleagues found that cultured parthenogenetic and androgenetic haploid embryonic stem cells (haESCs) display DNA hypomethylation resembling that of primordial germ cells. Through MII oocyte injection or sperm coinjection with hypomethylated haploid ESCs carrying specific imprinted region deletions, they obtained live bimaternal and bipaternal mice. Deletion of 3 imprinted regions in parthenogenetic haploid ESCs restored normal growth of fertile bimaternal mice, whereas deletion of 7 imprinted regions in androgenetic haploid ESCs enabled production of live bipaternal mice that died shortly after birth. Phenotypic analyses of organ and body size of these mice support the genetic conflict theory of genomic imprinting. Taken together, their results highlight the factors necessary for crossing same-sex reproduction barriers in mammals.

Read more, please click https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30441-7

2018年11月11日星期日

The Nobel Prize in Physiology or Medicine 1997

The Nobel Prize in Physiology or Medicine 1997 was awarded to Stanley B. Prusiner "for his discovery of Prions - a new biological principle of infection."

Stanley B. Prusiner

Born: 28 May 1942, Des Moines, IA, USA

Affiliation at the time of the award: University of California School of Medicine, San Francisco, CA, USA

Summary

The 1997 Nobel Prize in Physiology or Medicine is awarded to the American Stanley Prusiner for his pioneering discovery of an entirely new genre of disease-causing agents and the elucidation of the underlying principles of their mode of action. Stanley Prusiner has added prions to the list of well known infectious agents including bacteria, viruses, fungi and parasites. Prions exist normally as innocuous cellular proteins, however, prions possess an innate capacity to convert their structures into highly stabile conformations that ultimately result in the formation of harmful particles, the causative agents of several deadly brain diseases of the dementia type in humans and animals. Prion diseases may be inherited, laterally transmitted, or occur spontaneously. Regions within diseased brains have a characteristic porous and spongy appearance, evidence of extensive nerve cell death, and affected individuals exhibit neurological symptoms including impaired muscle control, loss of mental acuity, memory loss and insomnia. Stanley Prusiner’s discovery provides important insights that may furnish the basis to understand the biological mechanisms underlying other types of dementia-related diseases, for example Alzheimer’s disease, and establishes a foundation for drug development and new types of medical treatment strategies.

In 1972 Stanley Prusiner began his work after one of his patients died of dementia resulting from Creutzfeldt-Jakob disease (CJD). It had previously been shown that CJD, kuru, and scrapie, a similar disease affecting sheep, could be transmitted through extracts of diseased brains. There were many theories regarding the nature of the infectious agent, including one that postulated that the infectious agent lacked nucleic acid, a sensational hypothesis since at the time all known infectious agents contained the hereditary material DNA or RNA. Prusiner took up the challenge to precisely identify the infectious agent and ten years later in 1982 he and his colleagues successfully produced a preparation derived from diseased hamster brains that contained a single infectious agent. All experimental evidence indicated that the infectious agent was comprised of a single protein, and Prusiner named this protein a prion, an acronym derived from “proteinaceous infectious particle.” It should be noted that the scientific community greeted this discovery with great skepticism, however, an unwavering Prusiner continued the arduous task to define the precise nature of this novel infectious agent.



Please click https://www.nobelprize.org/prizes/medicine/1997/press-release/ for more detailed information.

Identification of spatially associated subpopulations by combining scRNAseq and sequential fluorescence in situ hybridization data

Content introduction:

  • Genome-wide screening for functional long noncoding RNAs in human cells by Cas9 targeting of splice sites

  • Identification of spatially associated subpopulations by combining scRNAseq and sequential fluorescence in situ hybridization data

  • De novo assembly of haplotype-resolved genomes with trio binning

  • An integrative tissue-network approach to identify and test human disease genes

  • High-quality genome sequences of uncultured microbes by assembly of read clouds


1. Genome-wide screening for functional long noncoding RNAs in human cells by Cas9 targeting of splice sites

The functions of many long noncoding RNAs (lncRNAs) in the human genome remain unknown owing to the lack of scalable loss-of-function screening tools. Ying Liu at Peking University in Beijing, China and her colleagues previously used pairs of CRISPR–Cas9 single guide RNAs (sgRNAs) for small-scale functional screening of lncRNAs4. Here they demonstrate genome-wide screening of lncRNA function using sgRNAs to target splice sites and achieve exon skipping or intron retention. Splice-site targeting outperformed a conventional CRISPR library in a negative selection screen targeting 79 ribosomal genes. Using a genome-scale library of splicing-targeting sgRNAs, they performed a screen covering 10,996 lncRNAs and identified 230 that are essential for cellular growth of chronic myeloid leukemia K562 cells. Screening GM12878 lymphoblastoid cells and HeLa cells with the same library identified cell-type-specific differences in lncRNA essentiality. Extensive validation confirmed the robustness of our approach.

Read more, please click https://www.nature.com/articles/nbt.4283

2. Identification of spatially associated subpopulations by combining scRNAseq and sequential fluorescence in situ hybridization data

How intrinsic gene-regulatory networks interact with a cell's spatial environment to define its identity remains poorly understood. Qian Zhu at Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health in Massachusetts, USA and his colleagues developed an approach to distinguish between intrinsic and extrinsic effects on global gene expression by integrating analysis of sequencing-based and imaging-based single-cell transcriptomic profiles, using cross-platform cell type mapping combined with a hidden Markov random field model. They applied this approach to dissect the cell-type- and spatial-domain-associated heterogeneity in the mouse visual cortex region. Their analysis identified distinct spatially associated, cell-type-independent signatures in the glutamatergic and astrocyte cell compartments. Using these signatures to analyze single-cell RNA sequencing data, they identified previously unknown spatially associated subpopulations, which were validated by comparison with anatomical structures and Allen Brain Atlas images.



Read more, please click https://www.nature.com/articles/nbt.4260

3. De novo assembly of haplotype-resolved genomes with trio binning

Complex allelic variation hampers the assembly of haplotype-resolved sequences from diploid genomes. Sergey Koren at National Human Genome Research Institute in Maryland, USA and his colleagues developed trio binning, an approach that simplifies haplotype assembly by resolving allelic variation before assembly. In contrast with prior approaches, the effectiveness of their method improved with increasing heterozygosity. Trio binning uses short reads from two parental genomes to first partition long reads from an offspring into haplotype-specific sets. Each haplotype is then assembled independently, resulting in a complete diploid reconstruction. They used trio binning to recover both haplotypes of a diploid human genome and identified complex structural variants missed by alternative approaches. They sequenced an F1 cross between the cattle subspecies Bos taurus taurus and Bos taurus indicus and completely assembled both parental haplotypes with NG50 haplotig sizes of >20 Mb and 99.998% accuracy, surpassing the quality of current cattle reference genomes. They suggest that trio binning improves diploid genome assembly and will facilitate new studies of haplotype variation and inheritance.

Read more, please click https://www.nature.com/articles/nbt.4277

4. An integrative tissue-network approach to identify and test human disease genes

Effective discovery of causal disease genes must overcome the statistical challenges of quantitative genetics studies and the practical limitations of human biology experiments. Here Victoria Yao at Princeton University in New Jersey, USA and his colleagues developed diseaseQUEST, an integrative approach that combines data from human genome-wide disease studies with in silico network models of tissue- and cell-type-specific function in model organisms to prioritize candidates within functionally conserved processes and pathways. They used diseaseQUEST to predict candidate genes for 25 different diseases and traits, including cancer, longevity, and neurodegenerative diseases. Focusing on Parkinson's disease (PD), a diseaseQUEST-directed Caenhorhabditis elegans behavioral screen identified several candidate genes, which they experimentally verified and found to be associated with age-dependent motility defects mirroring PD clinical symptoms. Furthermore, knockdown of the top candidate gene, bcat-1, encoding a branched chain amino acid transferase, caused spasm-like 'curling' and neurodegeneration in C. elegans, paralleling decreased BCAT1 expression in PD patient brains. diseaseQUEST is modular and generalizable to other model organisms and human diseases of interest.

Read more, please click https://www.nature.com/articles/nbt.4246

5. High-quality genome sequences of uncultured microbes by assembly of read clouds

Although shotgun metagenomic sequencing of microbiome samples enables partial reconstruction of strain-level community structure, obtaining high-quality microbial genome drafts without isolation and culture remains difficult. Here, Alex Bishara at Stanford University in California, USA and his colleagues present an application of read clouds, short-read sequences tagged with long-range information, to microbiome samples. They present Athena, a de novo assembler that uses read clouds to improve metagenomic assemblies. They applied this approach to sequence stool samples from two healthy individuals and compared it with existing short-read and synthetic long-read metagenomic sequencing techniques. Read-cloud metagenomic sequencing and Athena assembly produced the most comprehensive individual genome drafts with high contiguity (>200-kb N50, fewer than ten contigs), even for bacteria with relatively low (20×) raw short-read-sequence coverage. They also sequenced a complex marine-sediment sample and generated 24 intermediate-quality genome drafts (>70% complete, <10% contaminated), nine of which were complete (>90% complete, <5% contaminated). Their approach allows for culture-free generation of high-quality microbial genome drafts by using a single shotgun experiment.

Read more, please click https://www.nature.com/articles/nbt.4266