Evidence map›Paper›PMID 30254108›Full record

ArticleGenes & development2018

Single-nucleus transcriptomic survey of cell diversity and functional maturation in postnatal mammalian hearts.

Peng Hu, Jian Liu, Juanjuan Zhao, Benjamin J Wilkins, Katherine Lupino, Hao Wu, Liming Pei

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.

  1. Pooled it
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  12. Dissecting endothelial cell heterogeneity with new tools.Cell regeneration (London, England) · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. From Cell to Gene: Deciphering the Mechanism of Heart Failure With Single-Cell Sequencing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  18. Review
  19. Article
  20. Article

34 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Peng Hu *Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Jian Liu *Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Juanjuan Zhao *Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Benjamin J WilkinsDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Katherine LupinoCenter for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Hao WuCenter for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Liming PeiCenter for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.ORCID 0000-0002-1924-0333
Children's Hospital of Philadelphia · US

Funding

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
Coordinated regulation of mitochondrial and cellular functions by nuclear receptorsR01DK111495 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI PEI, LIMING · 2017 to 2021
$2.0M
Role of Cirhin/Utp4 in biliary development and diseaseK08DK099379 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI WILKINS, BENJAMIN J · 2014 to 2018
$737k
Genomic and functional analysis of active DNA demethylation in mammalian cellsR00HG007982 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI WU, HAO · 2016 to 2018
$732k
NHGRI NIH HHS R00 HG007982NHLBI NIH HHS DP2 HL142044NIDDK NIH HHS K08 DK099379NIDDK NIH HHS R01 DK111495
6 · The paper itself

Abstract

A fundamental challenge in understanding cardiac biology and disease is that the remarkable heterogeneity in cell type composition and functional states have not been well characterized at single-cell resolution in maturing and diseased mammalian hearts. Massively parallel single-nucleus RNA sequencing (snRNA-seq) has emerged as a powerful tool to address these questions by interrogating the transcriptome of tens of thousands of nuclei isolated from fresh or frozen tissues. snRNA-seq overcomes the technical challenge of isolating intact single cells from complex tissues, including the maturing mammalian hearts; reduces biased recovery of easily dissociated cell types; and minimizes aberrant gene expression during the whole-cell dissociation. Here we applied sNucDrop-seq, a droplet microfluidics-based massively parallel snRNA-seq method, to investigate the transcriptional landscape of postnatal maturing mouse hearts in both healthy and disease states. By profiling the transcriptome of nearly 20,000 nuclei, we identified major and rare cardiac cell types and revealed significant heterogeneity of cardiomyocytes, fibroblasts, and endothelial cells in postnatal developing hearts. When applied to a mouse model of pediatric mitochondrial cardiomyopathy, we uncovered profound cell type-specific modifications of the cardiac transcriptional landscape at single-nucleus resolution, including changes of subtype composition, maturation states, and functional remodeling of each cell type. Furthermore, we employed sNucDrop-seq to decipher the cardiac cell type-specific gene regulatory network (GRN) of GDF15, a heart-derived hormone and clinically important diagnostic biomarker of heart disease. Together, our results present a rich resource for studying cardiac biology and provide new insights into heart disease using an approach broadly applicable to many fields of biomedicine.

Indexed as

Gene Expression ProfilingTranscriptomeAnimalsCardiomyopathiesCell NucleusGene Regulatory NetworksGrowth Differentiation Factor 15HeartHigh-Throughput Nucleotide SequencingMiceMitochondrial DiseasesMyocardiumMyocytes, CardiacSequence Analysis, RNATranscriptional ActivationGdf15 protein, mouseGrowth Differentiation Factor 15ERRγGDF15mitochondrial cardiomyopathypostnatal heart maturationsingle-nucleus RNA-seq

Identifiers

PMID30254108
PMCPMC6169839
OpenAlexW2892550000

What OpenQuestion holds

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LicenceCC BY-NC
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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.