Current methods for epigenomic profiling are limited in their ability to obtain genome-wide information with spatial resolution. We introduce spatial ATAC, a method that integrates transposase-accessible chromatin profiling in tissue sections with barcoded solid-phase capture to perform spatially resolved epigenomics. We show that spatial ATAC enables the discovery of the regulatory programs underlying spatial gene expression during mouse organogenesis, lineage differentiation and in human pathology.
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http://dx.doi.org/10.1038/s41587-022-01603-9 | DOI Listing |
Objectives: Langerhans cells (LCs) are epithelial antigen-presenting cells (APC) contributing to immune surveillance. LCs depend on interleukin 34 (IL34) production by epithelial cells. This study aimed to uncover mechanisms of alteration of IL34 and LC function in squamous cell carcinoma (SCC).
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Genetics, Stanford School of Medicine, Stanford, CA 94305.
Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States. Familial adenomatous polyposis (FAP) is a hereditary syndrome that raises the risk of developing CRC, with total colectomy as the only effective prevention. Even though FAP is rare (0.
View Article and Find Full Text PDFNat Med
December 2024
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Successful pregnancy relies directly on the placenta's complex, dynamic, gene-regulatory networks. Disruption of this vast collection of intercellular and intracellular programs leads to pregnancy complications and developmental defects. In the present study, we generated a comprehensive, spatially resolved, multimodal cell census elucidating the molecular architecture of the first trimester human placenta.
View Article and Find Full Text PDFNat Commun
November 2024
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, Utrecht, the Netherlands.
Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic 'fetal' and WNT-high 'embryonal', displaying divergent WNT signaling patterns.
View Article and Find Full Text PDFCell Rep Methods
November 2024
Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104, USA. Electronic address:
Single-cell RNA sequencing has transformed the study of biological tissues by enabling transcriptomic characterizations of their constituent cell states. Computational methods for gene expression deconvolution use this information to infer the cell composition of related tissues profiled at the bulk level. However, current deconvolution methods are restricted to discrete cell types and have limited power to make inferences about continuous cellular processes such as cell differentiation or immune cell activation.
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