Evidence map›Paper›PMID 37640946›Full record

ArticleNature biotechnology2024

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects.

Emily B Fabyanic, Peng Hu, Qi Qiu, Kiara N Berríos, Daniel R Connolly, Tong Wang, Jennifer Flournoy, Zhaolan Zhou, Rahul M Kohli, Hao Wu

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 43 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Emily B Fabyanic *Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-7845-9653
Peng Hu *Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0017-1948
Qi Qiu *Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0933-4707
Kiara N BerríosPenn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA.
Daniel R ConnollyDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Tong WangPenn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4208-5578
Jennifer FlournoyDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Zhaolan ZhouDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Rahul M KohliPenn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-7689-5678
Hao WuDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, USA. haowu2@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0003-4395-6929
University of Pennsylvania · USPenn Center for AIDS Research · USShanghai Ocean University · CN

Funding

Defining causal roles of genomic variants on gene regulatory networks with spatiotemporally-resolved single-cell multiomicsU01HG012047 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI HONGJUN SONG, Hao Wu · 2021 to 2026
$7.1M
Understanding the Pathogenic Mechanisms of Rett SyndromeR01NS081054 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Zhaolan Zhou · 2013 to 2026
$5.6M
Ultra low-input epigenetic sequencing with combined enzymatic and long-read technologiesR01HG010646 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Gang Fang, Rahul Manu Kohli · 2019 to 2026
$3.9M
Charting oxygen-sensing gene regulatory network in cardiomyocytes through single-cell analysis and epigenome editingDP2HL142044 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI WU, HAO · 2017 to 2017
$2.4M
Understanding the Epigenetic Mechanisms Underlying Stress-related Neuropsychiatric DisordersR01MH111719 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI ZHOU, ZHAOLAN · 2018 to 2021
$2.2M
NHGRI NIH HHS R01 HG010646NHGRI NIH HHS U01 HG012047NHLBI NIH HHS DP2 HL142044NIMH NIH HHS R01 MH111719NINDS NIH HHS R01 NS081054U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) DP2-HL142044U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01-HG010646U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) U01-HG012047
6 · The paper itself

Abstract

Oxidative modification of 5-methylcytosine (5mC) by ten-eleven translocation (TET) DNA dioxygenases generates 5-hydroxymethylcytosine (5hmC), the most abundant form of oxidized 5mC. Existing single-cell bisulfite sequencing methods cannot resolve 5mC and 5hmC, leaving the cell-type-specific regulatory mechanisms of TET and 5hmC largely unknown. Here, we present joint single-nucleus (hydroxy)methylcytosine sequencing (Joint-snhmC-seq), a scalable and quantitative approach that simultaneously profiles 5hmC and true 5mC in single cells by harnessing differential deaminase activity of APOBEC3A toward 5mC and chemically protected 5hmC. Joint-snhmC-seq profiling of single nuclei from mouse brains reveals an unprecedented level of epigenetic heterogeneity of both 5hmC and true 5mC at single-cell resolution. We show that cell-type-specific profiles of 5hmC or true 5mC improve multimodal single-cell data integration, enable accurate identification of neuronal subtypes and uncover context-specific regulatory effects on cell-type-specific genes by TET enzymes.

Indexed as

5-MethylcytosineSingle-Cell AnalysisAnimalsBrainDNA MethylationEpigenesis, GeneticGene Expression RegulationHumansMice5-hydroxymethylcytosine5-Methylcytosine

Identifiers

PMID37640946
PMCPMC11525041
OpenAlexW4386215950

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.