Mammalian embryos exhibit sophisticated cellular patterning that is intricately orchestrated at both molecular and cellular level. It has recently become apparent that cells within the animal body display significant heterogeneity, both in terms of their cellular properties and spatial distributions. However, current spatial transcriptomic profiling either lacks three-dimensional representation or is limited in its ability to capture the complexity of embryonic tissues and organs. Here, we present a spatial transcriptomic atlas of all major organs at embryonic day 13.5 in the mouse embryo, and provide a three-dimensional rendering of molecular regulation for embryonic patterning with stacked sections. By integrating the spatial atlas with corresponding single-cell transcriptomic data, we offer a detailed molecular annotation of the dynamic nature of organ development, spatial cellular interactions, embryonic axes, and divergence of cell fates that underlie mammalian development, which would pave the way for precise organ engineering and stem cell-based regenerative medicine.
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http://dx.doi.org/10.1038/s41467-023-40155-7 | DOI Listing |
Nat Methods
January 2025
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often limited to one or two modalities, offering an incomplete view of cellular identity. Here we present spatial-Mux-seq, a multimodal spatial technology that allows simultaneous profiling of five different modalities: two histone modifications, chromatin accessibility, whole transcriptome and a panel of proteins at tissue scale and cellular level in a spatially resolved manner.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, the University of Tokyo, Tokyo, Japan.
Spatial transcriptomics is an essential application for investigating cellular structures and interactions and requires multimodal information to precisely study spatial domains. Here, we propose STAIG, a deep-learning model that integrates gene expression, spatial coordinates, and histological images using graph-contrastive learning coupled with high-performance feature extraction. STAIG can integrate tissue slices without prealignment and remove batch effects.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
Background: Cholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) and have been implicated in the immune response to cancer. However, the role and difference of TLSs and TILs in patients with cholangiocarcinoma remains unclear.
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
Institute of Bioinformatics and Applied Biotechnology, Bengaluru, Karnataka, India.
Alba domain-containing proteins are ubiquitously found in archaea and eukaryotes. By binding to either DNA, RNA, or DNA:RNA hybrids, these proteins function in genome stabilization, chromatin organization, gene regulation, and/or translational modulation. In the malaria parasite , six Alba domain proteins PfAlba1-6 have been described, of which PfAlba1 has emerged as a "master regulator" of translation during parasite intra-erythrocytic development (IED).
View Article and Find Full Text PDFCraniofacial development gives rise to the complex structures of the face and involves the interplay of diverse cell types. Despite its importance, our understanding of human-specific craniofacial developmental mechanisms and their genetic underpinnings remains limited. Here, we present a comprehensive single-nucleus RNA sequencing (snRNA-seq) atlas of human craniofacial development from craniofacial tissues of 24 embryos that span six key time points during the embryonic period (4-8 post-conception weeks).
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