Abstract 6604: Characterizing the tumor microenvironment using spatially barcoded archival FFPE tissue: converting single-nucleus RNA-seq into spatial transcriptomics

作者: Sakkos, Jonathan ; Wang, Wanxin ; Chang, Christina ; Fan, Christina ; Ngo, Bryant ; Uytingco, Cedric R. ; Wilhelmy, Julie

AbstractIdentifying the contribution and the role of each individual cell in the spatial context of the tumor microenvironment (TME) is crucial in determining tumor progression, examining the extent of immune infiltration, and identifying potential therapeutic targets. While single-cell sequencing-based techniques help reveal cellular heterogeneity in a cell population, they do not provide spatial context. In turn, recently emerged spatial transcriptomics techniques are challenged by the difficulty in pinpointing the spatial measurement to single cells, requiring either complex cell segmentation or deconvolution algorithms in the data processing.To address these limitations, we introduce Curio Trekker single-cell spatial mapping kit, a unique platform that turns a single-cell experiment into a spatial experiment, essentially providing a spatial measurement that has true single-cell resolution. It is based on the Slide-tags methodology (Russel et al, 2023) that spatially tags each nucleus within its native tissue environment. This approach utilizes existing single-nuclei sequencing infrastructure to generate high-resolution spatial transcriptomics data. Using archived FFPE samples, we demonstrate the effectiveness of Curio Trekker by aligning 25-30 µm tissue sections to spatially barcoded tiles. Spatial barcodes are cleaved and hybridized to cells and nuclei in the intact tissue, followed by tissue dissociation and nuclei isolation. The tagged nuclei are processed with established snRNA-seq workflows (e.g., 10x Chromium FLEX), producing gene expression and spatial libraries for the individual nuclei in the tissue section. This spatial tagging allows each nucleus to be bioinformatically mapped back to its original tissue location.We applied this solution to breast cancer biospecimens from different patients using whole transcriptome probes (10x Genomics). The resulting data allowed for detailed characterization of the TME, confidently identifying epithelial-malignant, stromal, and immune cells from each biospecimen. This enabled marker-guided regional selection and differential gene expression analysis based on both cell type and spatial location. Overall, the Curio Trekker platform provides a streamlined, high-resolution solution for profiling cellular heterogeneity and interactions within tumors, seamlessly integrating with existing workflows to generate rapid insights into disease mechanisms and therapeutic development.Citation Format:Cedric R. Uytingco, Julie Wilhelmy, Bryant Ngo, Jonathan Sakkos, Wanxin Wang, Christina Chang, Christina Fan. Characterizing the tumor microenvironment using spatially barcoded archival FFPE tissue: converting single-nucleus RNA-seq into spatial transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6604.

2017-07-01·Cancer Research

Abstract 5399: Investigating phenotypic plasticity in breast cancer with high-throughput nanogrid single-nucleus RNA sequencing

作者: Chan, Leo ; Yang, Jie ; Meric-Bernstam, Funda ; Sei, Emi ; Navin, Nicholas E. ; Kim, Charissa ; Gao, Ruli ; Srinivasan, Maithreyan ; Zhang, Hong

AbstractSingle-cell RNA sequencing (RNA-seq) is a powerful tool for investigating rare tumor subpopulations and resolving intra-tumor heterogeneity, but is low throughput, expensive, and requires fresh tissue samples. To address these limitations, we developed a 5’ high-throughput single-nucleus RNA sequencing (SNRS) approach that uses nanogrid technology to perform single-cell imaging and sequencing of 500-2500 nuclei in parallel. The automated image scanning procedure allowed us to exclude doublets and select live cells with DAPI/PI staining. This approach allows the transcriptomic profiling of frozen tissue samples, in which the cytoplasmic membrane is ruptured in cells, but leaves the nuclear membrane intact. We validated SNRS in a breast cancer cell line (SK-BR-3) and compared the transcriptomes of 500 nuclei to 500 whole cells, which revealed a high concordance in the number of genes expressed as well as their expression levels. We also performed bulk RNA-seq of isolated nuclear and cellular fractions from 5 breast cancer cell lines, which showed a high concordance in genes and expression levels. Differentially expressed genes in the nucleus mainly included lincRNAs, pseudogenes and mitochondria genes, but did not affect most cancer genes and pathway analysis. We further applied SNRS to sequence 500 nuclei from a triple-negative breast cancer patient and identified diverse phenotypes in tumor cells, including variation in cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition. These studies demonstrated the technical feasibility of using a nanogrid platform to perform high-throughput single-cell RNA sequencing and showed that nuclei from cell lines and tumors can be used to study signaling pathways and gene networks that play an important role in tumor progression.Citation Format: Ruli Gao, Charissa Kim, Emi Sei, Jie Yang, Leo Chan, Maithreyan Srinivasan, Hong Zhang, Funda Meric-Bernstam, Nicholas E. Navin. Investigating phenotypic plasticity in breast cancer with high-throughput nanogrid single-nucleus RNA sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5399. doi:10.1158/1538-7445.AM2017-5399

2017-07-01·Cancer Research

Abstract 486: Production of an unbiased, highly reproducible small RNA library for NGS using a novel circularization technology

作者: Kamberov, Emmanuel ; Ning, Jing ; Gonzalez-Plasky, Marta ; Hecker, Karl ; Charizanis, Konstantinos ; Carroll, Matthew ; Jan, Edward ; McNulty, Amanda

AbstractMicroRNA sequencing (miRNA-Seq) is a useful tool for aiding researchers in the examination of miRNA expression patterns, the characterization of novel miRNAs, and for uncovering miRNA-disease associations. Since miRNAs are also unusually well-preserved in a range of samples (e.g. urine, FFPE tissue, plasma), profiling their expression is becoming a powerful diagnostic tool. However, current methods for sequencing miRNA require large amounts of total RNA, are not very reproducible and, more importantly, have considerable systematic bias resulting in loss of many prospective biomarkers. This bias severely affects the trustworthiness of results as libraries are not a true representation of the biological state of the sample.We have recently developed a technology that efficiently captures miRNA species with extremely low bias. Through a circularization approach, Illumina P5 and P7 adapters are ligated to miRNA, resulting in sequenceable libraries in under 5 hours in a single tube. These libraries are then purified and size-selected prior to sequencing.Analysis of read distributions of libraries prepared from an equimolar mixture of 963 miRNAs demonstrated the technology is able to efficiently capture all species with high reproducibility between replicates and input amounts (correlation coefficient of ≥0.97). Furthermore, 80-86% of these captured miRNA read numbers fall within a +/- 2-fold variation of the expected read number demonstrating unbiased representation. In contrast, frequency distribution analyses for other technologies reveal that 47-56% of miRNAs are greatly under-represented (i.e. less than 2X fewer reads than expected), 29-38% of miRNAs are represented within a +/- 2-fold variation of the expected read number, and around 15% are over-represented by more than 2X.These findings highlight the fact that the current technical state of library preparation for miRNA sequencing fails to accurately represent miRNA expression patterns. This in turn leads researchers to perform more costly validation experiments than necessary. Our product is designed and developed for more accurately reflecting the true biological state of a sample. This will provide researchers with a tool that can aid in advancing miRNA sequencing in translational research.Note: This abstract was not presented at the meeting.Citation Format: Marta Gonzalez-Plasky, Amanda McNulty, Konstantinos Charizanis, Jing Ning, Edward Jan, Matthew Carroll, Emmanuel Kamberov, Karl Hecker. Production of an unbiased, highly reproducible small RNA library for NGS using a novel circularization technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 486. doi:10.1158/1538-7445.AM2017-486

项与 Takara Bio USA Holdings, Inc. 相关的新闻（医药）

2025-02-08

·宝日医

喜讯！Takara收购Curio Bioscience，并将业务扩展到空间组学分析！

Takara收购Curio Bioscience 日前，Takara Bio全资子公司Takara Bio USA Holdings, Inc.宣布完成对空间基因组学领域先驱公司Curio Bioscience的收购。这项战略性举措，把Curio Bioscience创新的空间生物学技术引入Takara Bio行业前沿的单细胞基因组学工具中，将为客户的空间生物学需求提供业界领先的解决方案。当前，基于下一代测序技术（NGS）的分析正迅速从Bulk测序分析转向单细胞分析，进而转向空间组学分析。单细胞分析可以明确单个细胞的基因表达状态，并能捕捉到基因的微小结构差异及其动态变化。空间组学分析则可以将组织中表达特定基因的细胞位置及其相互作用进行可视化，从而获得更详细的信息。顺应NGS的研究趋势，Takara Bio研发了用于NGS分析的SMARTer®系列试剂和单细胞分析仪Shasta™。此次收购Curio Bioscience，将利用Trekker这一真正意义上的单细胞空间分析技术，进一步扩展Takara Bio的NGS解决方案。 Curio Bioscience先进的Trekker技术用途广泛，无需专用设备即可应用于多种单细胞分析。它可以将空间信息与分子数据整合在一起，使研究人员能够将单细胞测序数据转化为空间解析图。通过这种转化，研究人员可以高分辨率地了解细胞在其原生组织环境中的组织和功能。 2025年1月15日起，Takara Bio开始在全球范围内销售Curio目前的产品系列。未来，Takara Bio也将进一步推进在空间组学分析领域的新产品开发和销售，为更尖端的生命科学研究提供支持！

并购

2025-01-15

·Business Wire

Takara Bio USA Holdings, Inc. Announces the Acquisition of Curio Bioscience, Adding Spatial Biology to Its Broad Portfolio of Single-Cell Omics Solutions

SAN JOSE, Calif.--( BUSINESS WIRE )--Takara Bio USA Holdings, Inc. (“TBUSH”) today announced the acquisition of Curio Bioscience, a pioneering company in the field of spatial genomics. This strategic acquisition combines two innovative spatial biology platforms with Takara Bio’s industry-leading portfolio of single-cell genomics tools. TBUSH is a wholly owned subsidiary of Takara Bio Inc. ("Takara Bio"), a leading global biotechnology and life science company headquartered in Shiga, Japan. Takara Bio USA , Inc. ("TBUSA") is a wholly owned subsidiary of TBUSH. TBUSA and TBUSH are part of the global Takara Bio Group, which offers diverse life science products and services supporting discovery, translational, and clinical scientists in advancing their research. The Curio Bioscience acquisition will extend the power of Takara Bio’s NGS solutions and give customers deeper insights into tissue spatial organization and molecular composition. “We are proud of our history of innovation in the single-cell genomics market, having developed the first commercially available kits for single-cell RNA- and DNA-seq,” said Carol Lou, President and CEO of Takara Bio USA. “The acquisition of Curio Bioscience continues this legacy with the addition of Trekker, the first truly single-cell spatial technology.” Curio’s advanced Trekker and Seeker technologies integrate spatial information with molecular data, enabling researchers to transform single-cell sequencing data into spatially resolved maps. This transformation offers high-resolution insights into the organization and function of cells within their native tissue environments. “Curio Bioscience is dedicated to creating innovative approaches that map the entire transcriptome with unparalleled sensitivity and resolution,” said Stephen Fodor, co-founder and CEO. “Combining Curio’s technology with Takara Bio’s vast NGS and single-cell tool set will provide customers with industry-leading solutions for their spatial biology needs.” Through these advancements, Takara Bio has solidified its position as a leader in the single-cell genomics market by continually driving innovation and supporting groundbreaking research in the life science market for a wide range of applications in cancer biology, neuroscience, developmental biology, and immunology. Advisors Houlihan Lokey acted as exclusive financial advisor and Cooley LLP acted as legal advisor to Takara Bio. Aquilo Partners, L.P. acted as financial advisor and Dorsey & Whitney LLP as legal advisor to Curio Bioscience. About Takara Bio Takara Bio USA, Inc. is a wholly owned subsidiary of Takara Bio Inc. that manufactures and distributes kits, reagents, and instruments for the life sciences, including NGS, PCR, gene delivery, genome editing, stem cell research, nucleic acid and protein purification, and automated sample preparation. Takara Bio Inc., a world leader in biotechnology research and development, offers a host of life science research solutions, from enzymes and GMP-grade reagents to contracted cell and gene therapy manufacturing services and is the developer of the RetroNectin® reagent, a world standard in gene therapy protocols. Takara Bio is committed to preventing disease and improving the quality of life for all people through the use of biotechnology. For more information, visit takarabio.com . About Curio Bioscience Curio Bioscience is advancing a new generation of high-precision tools for the life sciences industry. The company has developed innovative spatial biology capabilities to map the whole transcriptome at high resolution using existing sequencing workflows and instrumentation. The founding team has a strong track record of bringing genomic solutions to market. Curio Bioscience is based in Palo Alto, California.

并购

2025-01-14

·SYNAPSE

Takara Bio USA Holdings, Inc. announces the acquisition of Curio Bioscience, adding spatial biology to its broad portfolio of single-cell omics solutions

Takara Bio USA Holdings, Inc. (“TBUSH”) today announced the acquisition of Curio Bioscience, a pioneering company in the field of spatial genomics. This strategic acquisition combines two innovative spatial biology platforms with Takara Bio’s industry-leading portfolio of single-cell genomics tools. TBUSH is a wholly owned subsidiary of Takara Bio Inc. ("Takara Bio"), a leading global biotechnology and life science company headquartered in Shiga, Japan. Takara Bio USA, Inc. ("TBUSA") is a wholly owned subsidiary of TBUSH. TBUSA and TBUSH are part of the global Takara Bio Group, which offers diverse life science products and services supporting discovery, translational, and clinical scientists in advancing their research. The Curio Bioscience acquisition will extend the power of Takara Bio’s NGS solutions and give customers deeper insights into tissue spatial organization and molecular composition. “We are proud of our history of innovation in the single-cell genomics market, having developed the first commercially available kits for single-cell RNA- and DNA-seq,” said Carol Lou, President and CEO of Takara Bio USA. “The acquisition of Curio Bioscience continues this legacy with the addition of Trekker, the first truly single-cell spatial technology.” Curio’s advanced Trekker and Seeker technologies integrate spatial information with molecular data, enabling researchers to transform single-cell sequencing data into spatially resolved maps. This transformation offers high-resolution insights into the organization and function of cells within their native tissue environments. “Curio Bioscience is dedicated to creating innovative approaches that map the entire transcriptome with unparalleled sensitivity and resolution,” said Stephen Fodor, co-founder and CEO. “Combining Curio’s technology with Takara Bio’s vast NGS and single-cell tool set will provide customers with industry-leading solutions for their spatial biology needs.” Through these advancements, Takara Bio has solidified its position as a leader in the single-cell genomics market by continually driving innovation and supporting groundbreaking research in the life science market for a wide range of applications in cancer biology, neuroscience, developmental biology, and immunology. Advisors Houlihan Lokey acted as exclusive financial advisor and Cooley LLP acted as legal advisor to Takara Bio. Aquilo Partners, L.P. acted as financial advisor and Dorsey & Whitney LLP as legal advisor to Curio Bioscience.

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100 项与 Takara Bio USA Holdings, Inc. 相关的药物交易

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100 项与 Takara Bio USA Holdings, Inc. 相关的转化医学

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