---
_id: '12106'
abstract:
- lang: eng
text: Regulation of chromatin states involves the dynamic interplay between different
histone modifications to control gene expression. Recent advances have enabled
mapping of histone marks in single cells, but most methods are constrained to
profile only one histone mark per cell. Here, we present an integrated experimental
and computational framework, scChIX-seq (single-cell chromatin immunocleavage
and unmixing sequencing), to map several histone marks in single cells. scChIX-seq
multiplexes two histone marks together in single cells, then computationally deconvolves
the signal using training data from respective histone mark profiles. This framework
learns the cell-type-specific correlation structure between histone marks, and
therefore does not require a priori assumptions of their genomic distributions.
Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single
cells across a range of mark combinations. Modeling dynamics of in vitro macrophage
differentiation enables integrated analysis of chromatin velocity. Overall, scChIX-seq
unlocks systematic interrogation of the interplay between histone modifications
in single cells.
acknowledgement: We thank M. van Loenhout for experimental advice on purifying cell
types from the bone marrow, R. van der Linden for expertise with FACS and M. Blotenburg
for help with cell typing the mouse organogenesis dataset. We thank M. Saraswat
and O. Stegle for discussions on multinomial distributions. This work was supported
by a European Research Council Advanced grant (ERC-AdG 742225-IntScOmics); Nederlandse
Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP grant (NWO CW 714.016.001)
and NWO grant (OCENW.GROOT.2019.017); the Swiss National Science Foundation Early
Postdoc Mobility (P2ELP3-184488 to P.Z. and P2BSP3-174991 to J.Y.); Marie Sklodowska-Curie
Actions Postdoc (798573 to P.Z.) and the Human Frontier for Science Program Long-Term
Fellowships (LT000209-2018-L to P.Z. and LT000097-2019-L to J.Y.). This work is
part of the Oncode Institute which is financed partly by the Dutch Cancer Society.
article_processing_charge: No
article_type: original
author:
- first_name: Jake
full_name: Yeung, Jake
id: 123012b2-db30-11eb-b4d8-a35840c0551b
last_name: Yeung
orcid: 0000-0003-1732-1559
- first_name: Maria
full_name: Florescu, Maria
last_name: Florescu
- first_name: Peter
full_name: Zeller, Peter
last_name: Zeller
- first_name: Buys Anton
full_name: De Barbanson, Buys Anton
last_name: De Barbanson
- first_name: Max D.
full_name: Wellenstein, Max D.
last_name: Wellenstein
- first_name: Alexander
full_name: Van Oudenaarden, Alexander
last_name: Van Oudenaarden
citation:
ama: Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden
A. scChIX-seq infers dynamic relationships between histone modifications in single
cells. Nature Biotechnology. 2023;41:813–823. doi:10.1038/s41587-022-01560-3
apa: Yeung, J., Florescu, M., Zeller, P., De Barbanson, B. A., Wellenstein, M. D.,
& Van Oudenaarden, A. (2023). scChIX-seq infers dynamic relationships between
histone modifications in single cells. Nature Biotechnology. Springer Nature.
https://doi.org/10.1038/s41587-022-01560-3
chicago: Yeung, Jake, Maria Florescu, Peter Zeller, Buys Anton De Barbanson, Max
D. Wellenstein, and Alexander Van Oudenaarden. “ScChIX-Seq Infers Dynamic Relationships
between Histone Modifications in Single Cells.” Nature Biotechnology. Springer
Nature, 2023. https://doi.org/10.1038/s41587-022-01560-3.
ieee: J. Yeung, M. Florescu, P. Zeller, B. A. De Barbanson, M. D. Wellenstein, and
A. Van Oudenaarden, “scChIX-seq infers dynamic relationships between histone modifications
in single cells,” Nature Biotechnology, vol. 41. Springer Nature, pp. 813–823,
2023.
ista: Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden
A. 2023. scChIX-seq infers dynamic relationships between histone modifications
in single cells. Nature Biotechnology. 41, 813–823.
mla: Yeung, Jake, et al. “ScChIX-Seq Infers Dynamic Relationships between Histone
Modifications in Single Cells.” Nature Biotechnology, vol. 41, Springer
Nature, 2023, pp. 813–823, doi:10.1038/s41587-022-01560-3.
short: J. Yeung, M. Florescu, P. Zeller, B.A. De Barbanson, M.D. Wellenstein, A.
Van Oudenaarden, Nature Biotechnology 41 (2023) 813–823.
corr_author: '1'
date_created: 2023-01-08T23:00:53Z
date_published: 2023-06-01T00:00:00Z
date_updated: 2025-04-23T08:45:24Z
day: '01'
ddc:
- '570'
department:
- _id: ScienComp
doi: 10.1038/s41587-022-01560-3
external_id:
isi:
- '000909067600003'
pmid:
- '36593403'
file:
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creator: dernst
date_created: 2023-08-16T11:30:45Z
date_updated: 2023-08-16T11:30:45Z
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intvolume: ' 41'
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language:
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month: '06'
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oa_version: Published Version
page: 813–823
pmid: 1
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: scChIX-seq infers dynamic relationships between histone modifications in single
cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 41
year: '2023'
...