Spatial-CUT&Tag: Spatially resolved chromatin modification profiling at the cellular level

Author:

Deng Yanxiang12ORCID,Bartosovic Marek3,Kukanja Petra3ORCID,Zhang Di1ORCID,Liu Yang12ORCID,Su Graham12ORCID,Enninful Archibald12ORCID,Bai Zhiliang1ORCID,Castelo-Branco Gonçalo34ORCID,Fan Rong125ORCID

Affiliation:

1. Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

2. Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.

3. Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.

4. Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.

5. Human and Translational Immunology Program, Yale School of Medicine, New Haven, CT 06520, USA.

Abstract

Spatial omics emerged as a new frontier of biological and biomedical research. Here, we present spatial-CUT&Tag for spatially resolved genome-wide profiling of histone modifications by combining in situ CUT&Tag chemistry, microfluidic deterministic barcoding, and next-generation sequencing. Spatially resolved chromatin states in mouse embryos revealed tissue-type-specific epigenetic regulations in concordance with ENCODE references and provide spatial information at tissue scale. Spatial-CUT&Tag revealed epigenetic control of the cortical layer development and spatial patterning of cell types determined by histone modification in mouse brain. Single-cell epigenomes can be derived in situ by identifying 20-micrometer pixels containing only one nucleus using immunofluorescence imaging. Spatial chromatin modification profiling in tissue may offer new opportunities to study epigenetic regulation, cell function, and fate decision in normal physiology and pathogenesis.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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