populates the striatum but not the corpus
callosum or cortex. In addition, the epigenetic
state associated with protoplasmic astrocytes
(ACTE2) is mainly localized in the corpus
callosum, although it was also observed in the
cortex and striatum at lower frequencies.
Our study demonstrates the profiling of
chromatin states in situ in tissue sections
with high spatial resolution. Although spatial-
CUT&Tag focuses on the tissue mapping of
histone modifications, integration with other
assays such as transcriptome and proteins is
feasible with our microfluidic in tissue bar-
coding approach by combining reagents for
DBiT-seq ( 12 ) and spatial-CUT&Tag to achieve
spatial multi-omics profiling. Moreover, the
mapping area could be further increased by
using a serpentine microfluidic channel or
increasing the number of barcodes (e.g., 100 ×
100). Spatial-CUT&Tag is a next-generation
sequencing–based approach, which is unbiased
for genome-wide mapping of epigenetic mech-
anisms in the tissue context.
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ACKNOWLEDGMENTS
We thank T. Jimenez-Beristain in the GCB laboratory for writing
laboratory animal ethics permit 1995_2019 and for assistance with
animal experiments. We also thank the Yale Center for Research
Computing for guidance and use of the research computing
infrastructure. The molds for microfluidic chips were fabricated at
the Yale University School of Engineering and Applied Science
(SEAS) Nanofabrication Center. We used the service provided by
the Genomics Core of Yale Cooperative Center of Excellence
in Hematology (U54DK106857). Next-generation sequencing was
conducted at Yale Stem Cell Center Genomics Core Facility,
which was supported by the Connecticut Regenerative MedicineResearch Fund and the Li Ka Shing Foundation.Funding:This
research was supported by a Packard Fellowship for Science and
Engineering (to R.F.); a Yale Stem Cell Center Chen Innovation
Award (to R.F.); and the National Institutes of Health (NIH) (grants
U54CA209992, R01CA245313, UG3CA257393, and RF1MH128876
to R.F.). This material is based in part upon work supported
under a collaboration by Stand Up To Cancer, a program of
the Entertainment Industry Foundation and the Society for
Immunotherapy of Cancer (to R.F. and Y.L.). The work in G.C.-B’s
research group was supported by the Swedish Research
Council (grant 2019-01360), the European Union (Horizon 2020
Research and Innovation Programme/European Research
Council Consolidator EPIScOPE grant 681893), the Swedish
Cancer Society (Cancerfonden grant 190394 Pj), the Knut and
Alice Wallenberg Foundation (grants 2019-0107 and 2019-0089),
the Swedish Society for Medical Research (grant JUB2019),
the Ming Wai Lau Center for Reparative Medicine, and the
Karolinska Institutet.Author contributions:Conceptualization:
R.F.; Data analysis: Y.D., M.B., G.C.-B., R.F.; Investigation: Y.D.,
P.K., and D.Z.; Methodology: Y.D., D.Z., and Y.L.; Resources: G.S.,
A.E., and Z.B.; Writing–original draft: Y.D. and R.F. All authors
reviewed, edited, and approved the manuscript.Competing
interests:R.F. and Y.D. are inventors of a patent application
related to this work. R.F. is scientific founder and adviser
for IsoPlexis, Singleron Biotechnologies, and AtlasXomics. The
interests of R.F. were reviewed and managed by Yale University
Provost’s Office in accordance with the University’s conflict
of interest policies.Data and materials availability:The
sequencing data reported in this paper are deposited in the
Gene Expression Omnibus (GEO) with accession code GSE165217.
Code for sequencing data analysis is available on Zenodo ( 26 ).SUPPLEMENTARY MATERIALS
science.org/doi/10.1126/science.abg7216
Materials and Methods
Figs. S1 to S18
Tables S1 to S3
References ( 27 – 35 )
MDAR Reproducibility Checklist
23 January 2021; resubmitted 11 October 2021
Accepted 12 January 2022
10.1126/science.abg7216686 11 FEBRUARY 2022•VOL 375 ISSUE 6581 science.orgSCIENCE
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