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Biotechnology & Applied Microbiology
Yang Liu et al.
Summary: In this study, the researchers extended the co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and successfully mapped a large number of proteins and the whole transcriptome. They applied this method to analyze multiple mouse tissue types and human tissues, revealing spatially distinct reactions and immune activation. The co-indexing of transcriptomes and epitopes in the spatial dimension with large protein panels proved to be effective.
NATURE BIOTECHNOLOGY
(2023)
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Multidisciplinary Sciences
Yanxiang Deng et al.
Summary: Spatial omics has become a new frontier in biological and biomedical research. In this study, we introduce spatial-CUT&Tag, which combines in situ CUT&Tag chemistry, microfluidic deterministic barcoding, and next-generation sequencing for spatially resolved genome-wide profiling of histone modifications. Our findings in mouse embryos reveal tissue-specific epigenetic regulations and provide spatial information at tissue scale. Additionally, spatial-CUT&Tag allows us to uncover the epigenetic control of cortical layer development and spatial patterning of cell types in the mouse brain. This technique also enables the in situ derivation of single-cell epigenomes.
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Cell Biology
Suwei Gao et al.
Summary: This study identified novel transcriptionally heterogeneous subsets of HSC/MPP in mouse fetal liver, including a CD93-enriched subset with enhanced stem cell properties, as well as 'pocket-like' units called HSC PLUS enriched with growth factors and niche cells. Unexpectedly, macrophages were found to play a supportive role in HSC/MPP expansion, along with growth factors such as MDK, PTN, and IGFBP5. Furthermore, while conserved cell-cell interactions and expansion mechanisms were observed between mouse and human FL HSCs/MPPs, their transcriptome signatures showed divergence.
Article
Biochemistry & Molecular Biology
Ao Chen et al.
Summary: Spatially resolved transcriptomic technologies enable us to study complex biological processes such as mammalian embryogenesis. However, current methods have limitations in resolution, gene capture, and field of view, which hinders their systematic application to large and three-dimensional mid- and late-gestation embryos. In this study, we developed Stereo-seq, a spatially enhanced resolution omics-sequencing method, by combining DNA nanoball-patterned arrays and in situ RNA capture. We used Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas, MOSTA, which provides single cell resolution and high sensitivity for mapping the kinetics and directionality of transcriptional variation during mouse organogenesis. By utilizing this atlas, we investigated the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues like the dorsal midbrain. Our panoramic atlas will facilitate in-depth research into long-standing questions about normal and abnormal mammalian development.
Article
Immunology
Maxime Meylan et al.
Summary: The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in renal cell carcinoma (RCC). B cells are enriched in TLS and demonstrate diverse maturation stages, with the presence of fully mature clonotypes. Additionally, IgG-and IgA-producing plasma cells (PCs) disseminate into the tumor beds along fibroblastic tracks in TLS+ tumors, indicating potential anti-tumor effector activity. Furthermore, the presence of IgG-stained tumor cells correlates with therapeutic responses and progression-free survival in RCC patients treated with immune checkpoint inhibitors.
Article
Multidisciplinary Sciences
Yanxiang Deng et al.
Summary: This study presents a new method for spatial chromatin accessibility profiling in tissues, allowing researchers to explore the spatial epigenetic information at the cellular level and genome scale. The technology has been successfully applied to understand gene regulators in the development of the central nervous system and immune cell types in tonsil tissue. This advancement in spatial biology improves our understanding of cell identity, cell state, and cell fate decision in relation to epigenetic underpinnings in development and disease.
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Oncology
Yeh Wang et al.
Summary: By analyzing the precursor stage and cancer tissue of high-grade serous carcinoma (HGSC) in the ovary, researchers have identified the role of IGFBP2 in driving tumor initiation, providing new insights into ovarian cancer development.
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Neurosciences
Jessica M. Noll et al.
Summary: This study used digital spatial profiling technology to investigate the cellular and neuroinflammatory mechanisms early after ischemic stroke. The results showed distinct proteomic profiles in different spatial regions of the affected brain hemisphere, which correlated with immunohistochemical markers. The core border region demonstrated induction of neuronal death, apoptosis, autophagy, immunoreactivity, and early degenerative proteins, while the peri-infarct region showed increased astrocytic, apoptotic, and neurodegenerative proteomic profiles. Minimal changes were observed in the peri-infarct normal tissue region.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Jingjin Sun et al.
Summary: The study investigates the neurobiological mechanism of repetitive behaviors in mice and identifies the role of MPLSST neurons in self-grooming and anxiety regulation. Activation of MPLSST neurons promotes rewarding effects and activates dopamine neurons, while loss of function impairs self-grooming and post-stress anxiety alleviation. The findings suggest a dual role of the CeA-MPLSST-VTA-DA circuit in stress and reward processing.
Article
Oncology
Vinay Kumar et al.
Summary: In prostate cancer, the tumor microenvironment plays a crucial role in the development and progression of the disease. This study utilized Digital Spatial Profiling multiplex technology to assess the expression of proteins and RNA transcripts in challenging samples. The results revealed differences in protein and RNA expression among different cell types and validated the protein expression in a larger cohort of prostate cancer patients. Furthermore, closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.
Article
Cell Biology
Jaejun Lee et al.
Summary: This study utilized multiplexed digital spatial protein profiling to develop a unique protein signature predicting advanced liver fibrosis. Through single-cell RNA sequencing analysis and protein-based multiplexed profiling, the study revealed the phenotypic differences of portal MPs between livers with early- or late-stage fibrosis.
Article
Biochemistry & Molecular Biology
Xiaonan Fu et al.
Summary: This study introduces a stamping method for fabricating polony gels, reducing the cost and time of barcode sequencing, and developing a single-cell spatial transcriptomic assay. This method offers high resolution and RNA capture efficiency for mapping and analyzing cell-cell communication in tissues.
Article
Biotechnology & Applied Microbiology
Robert R. Stickels et al.
Summary: Slide-seqV2 technology achieves an RNA capture efficiency close to 50% of single-cell RNA-seq data, which is 10 times higher than Slide-seq and approaches the detection efficiency of droplet-based single-cell RNA-seq techniques. Leveraging the high detection efficiency of Slide-seqV2, dendritically localized mRNAs in mouse hippocampal neurons were successfully identified, and spatial information was integrated with single-cell trajectory analysis tools to characterize the spatiotemporal development of the mouse neocortex, revealing underlying genetic programs that were poorly sampled with Slide-seq. The combination of near-cellular resolution and high transcript detection efficiency makes Slide-seqV2 applicable across various experimental contexts.
NATURE BIOTECHNOLOGY
(2021)
Article
Biochemical Research Methods
Chenxu Zhu et al.
Summary: Genome-wide profiling of histone modifications can provide insights into regulatory elements, cell-type-specific gene expression, and epigenetic regulatory mechanisms. An ultra-high-throughput method, Paired-Tag, allows joint profiling of histone modifications and transcriptome at single-cell resolution. Integrative analysis of the data reveals distinct groups of genes subject to divergent epigenetic regulatory mechanisms.
Article
Neurosciences
Kristen R. Maynard et al.
Summary: This study defined spatial gene expression in the human dorsolateral prefrontal cortex, revealing layer-enriched expression of genes associated with schizophrenia and autism, highlighting the clinical relevance of spatially defined expression.
NATURE NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Yang Wang et al.
Summary: Extensive epigenetic reprogramming occurs during preimplantation embryo development. Researchers have developed a single-cell multiomics sequencing technology for profiling chromatin accessibility, DNA methylation, and RNA expression in individual cells, enabling the study of genetic lineages reconstruction and regulatory networks in early embryos.
NATURE COMMUNICATIONS
(2021)
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Multidisciplinary Sciences
Rui Wu et al.
Summary: The study constructed a high-resolution spatial transcriptome map of primary liver cancers and revealed the evolution of tumor microenvironment characteristics from nontumor to tumor regions. It proposed a signature for accurately locating tertiary lymphoid structures spatially and identified interactions related to TME remodeling and tumor metastasis.
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Multidisciplinary Sciences
Andre F. Rendeiro et al.
Summary: Recent studies using high-parameter imaging mass cytometry have provided insights into the cellular composition and spatial architecture of acute lung injury in humans, including injuries derived from SARS-CoV-2 infection. It was found that SARS-CoV-2 predominantly infects alveolar epithelial cells and induces a localized hyperinflammatory cell state associated with lung damage. As COVID-19 progresses, there is increased macrophage extravasation, along with increased numbers of mesenchymal cells and fibroblasts, possibly indicating attempts to repair the damaged lung tissue. The data generated help in developing a biologically interpretable landscape of lung pathology at both macroscopic and single-cell levels, providing a basis for understanding COVID-19 and lung pathology.
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Biochemistry & Molecular Biology
Chun-Seok Cho et al.
Summary: Seq-Scope is a spatial barcoding technology with resolution comparable to an optical microscope, allowing visualization of spatial transcriptome heterogeneity at multiple histological scales from tissue sections. The technology works by processing DNA clusters to expose RNA-capture moiety, making cell analysis simpler and more accurate.
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Cell Biology
Jesper Baeckdahl et al.
Summary: By studying the composition and structure of WAT, we identified that human WAT is composed of three classes of mature adipocytes, only one of which is insulin responsive.
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Rebecca A. Porritt et al.
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CIRCULATION RESEARCH
(2021)
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Genetics & Heredity
Sunny Z. Wu et al.
Summary: This study presents a comprehensive transcriptional atlas of the cellular architecture of breast cancer, identifying recurrent neoplastic cell heterogeneity and new immune cell populations associated with clinical outcomes. A multi-omic atlas integrates single-cell RNA sequencing, spatial transcriptomics, and immunophenotyping to stratify breast cancer into nine ecotypes with unique cellular compositions and clinical outcomes.
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Neurosciences
Philip Hasel et al.
Summary: This study investigated the transcriptome changes of mouse cortical astrocytes after an acute inflammatory stimulus, revealing rapid and drastic changes over time. By sequencing thousands of astrocytes at single-cell resolution, it was shown that inflammation causes a widespread response with distinct subtypes undergoing inflammatory transitions with defined transcriptomic profiles. Spatial transcriptomics and in situ hybridization were used to attribute specific inflammation-induced reactive astrocyte sub-states to certain brain regions.
NATURE NEUROSCIENCE
(2021)
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Multidisciplinary Sciences
Sanjay R. Srivatsan et al.
Summary: The study introduces a method called sci-Space, which allows for spatial heterogeneity analysis at larger scales while retaining single-cell resolution. By applying this method to developing mouse embryos, the researchers identified thousands of genes exhibiting anatomically patterned expression and leveraged spatial information to annotate cellular subtypes. The results show substantial variation in spatial patterning among cell types and reveal correlations between pseudotime and the migratory patterns of differentiating neurons.
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Multidisciplinary Sciences
Kenneth H. Gouin et al.
Summary: The study identified an epithelial subpopulation in bladder cancer with therapeutic response prediction ability through single nuclei RNA sequencing and spatial analysis, indicating CDH12-enriched tumors have poor outcome following surgery but superior response to ICT. This study provides a potential framework for designing biomarker-guided clinical trials in bladder cancer therapeutics.
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