Academic Journal

Transcriptional dynamics of the murine heart during perinatal development at single-cell resolution.

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Title: Transcriptional dynamics of the murine heart during perinatal development at single-cell resolution.
Authors: Feulner L; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; University of Montreal, Department of Molecular Biology, Montreal, QC H3T 1J4, Canada., Wünnemann F; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; Institute for Computational Biomedicine, Faculty of Medicine, University Hospital Heidelberg and Heidelberg University, 69120 Heidelberg, Germany., Rafatian N; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada., Liang J; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; McGill University, Department of Anatomy and Cell Biology, Montreal, QC H3A 0G4, Canada., Medouni A; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; McGill University, Department of Anatomy and Cell Biology, Montreal, QC H3A 0G4, Canada., Hofmann P; German Centre for Cardiovascular Research, Institute of Medical Genetics, Carl von Ossietzky University, 26129 Oldenburg, Germany., Hitz MP; German Centre for Cardiovascular Research, Institute of Medical Genetics, Carl von Ossietzky University, 26129 Oldenburg, Germany., Schapiro D; Institute for Computational Biomedicine, Faculty of Medicine, University Hospital Heidelberg and Heidelberg University, 69120 Heidelberg, Germany., Leclerc S; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; Centre Hospitalier de I'Université de Montreal (CHUM) Research Centre, OPTILAB Diagnostic Laboratory, Montreal, QC H2X 0C1, Canada., van Vliet PP; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada., Andelfinger G; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.
Source: Biology open [Biol Open] 2026 Sep 15; Vol. 15 (9). Date of Electronic Publication: 2026 Sep 11.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101578018 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2046-6390 (Electronic) Linking ISSN: 20466390 NLM ISO Abbreviation: Biol Open Subsets: MEDLINE
Imprint Name(s): Original Publication: Cambridge : Company of Biologists Ltd.
MeSH Terms: Single-Cell Analysis*/methods , Heart*/embryology , Heart*/growth & development , Myocardium*/metabolism , Gene Expression Regulation, Developmental* , Transcription, Genetic*, RNA, Long Noncoding/genetics ; Endothelial Cells/metabolism ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Computational Biology/methods ; Animals ; Mice ; Humans ; Single-Cell Gene Expression Analysis ; Gene Expression Profiling ; Transcriptome
Abstract: Heart maturation and remodelling during the foetal and early postnatal period are critical for the proper survival and growth of the foetus, yet our knowledge of the molecular processes involved is lacking for many cardiac cell types. To gain a deeper understanding of the transcriptional dynamics of the heart during the perinatal period, we performed single-cell RNA sequencing on foetal and early postnatal mouse hearts to establish a catalogue of 49,769 single-cell transcriptomes and used this for bioinformatics analyses. Pseudotime analyses and RNAscope fluorescence in situ hybridisation showed that while lncRNA H19 expression decreased over time in multiple cardiac cell types, it remained stably expressed in endocardial and valve endothelial cells. To further investigate this in a human setting, we generated human induced pluripotent stem cell (hiPSC)-derived endothelial cells and used single-cell data to develop a sorting strategy to separate endocardial from vascular endothelial cells, ensuring endothelial subtype purity. Knockdown of H19 in hiPSC-derived endocardial cells resulted in morphological changes, decreased expression of endothelial markers, and increased expression of mesenchymal markers, consistent with the onset of endothelial-to-mesenchymal transition. Together, our data suggest a role for H19 in maintaining endocardial and valve endothelial cell states during perinatal heart maturation.
(© 2026. Published by The Company of Biologists.)
Competing Interests: Competing interests The authors declare no competing or financial interests.
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Grant Information: G-17-0019170 Heart and Stroke Foundation of Canada; MIBAVA-Leducq 12CVD03 Fondation Leducq; Nationale Bank van België; 453653 Canada CAPMC CIHR; 27335 Fonds de Recherche du Québec - Sante; Deutsche Forschungsgemeinschaft; BMBF 01ZZ2004 German Federal Ministry of Education and Research
Contributed Indexing: Keywords: Endocardial development; H19; Heart maturation; Perinatal; Single-cell RNA-seq; Valve development
Substance Nomenclature: 0 (RNA, Long Noncoding)
0 (H19 long non-coding RNA)
Entry Date(s): Date Created: 20260911 Date Completed: 20260911 Latest Revision: 20260926
Update Code: 20260926
PubMed Central ID: PMC13602375
DOI: 10.1242/bio.062493
PMID: 42725465
Database: MEDLINE
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  Data: Transcriptional dynamics of the murine heart during perinatal development at single-cell resolution.
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  Data: <searchLink fieldCode="AU" term="%22Feulner+L%22">Feulner L</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; University of Montreal, Department of Molecular Biology, Montreal, QC H3T 1J4, Canada.<br /><searchLink fieldCode="AU" term="%22Wünnemann+F%22">Wünnemann F</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; Institute for Computational Biomedicine, Faculty of Medicine, University Hospital Heidelberg and Heidelberg University, 69120 Heidelberg, Germany.<br /><searchLink fieldCode="AU" term="%22Rafatian+N%22">Rafatian N</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.<br /><searchLink fieldCode="AU" term="%22Liang+J%22">Liang J</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; McGill University, Department of Anatomy and Cell Biology, Montreal, QC H3A 0G4, Canada.<br /><searchLink fieldCode="AU" term="%22Medouni+A%22">Medouni A</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; McGill University, Department of Anatomy and Cell Biology, Montreal, QC H3A 0G4, Canada.<br /><searchLink fieldCode="AU" term="%22Hofmann+P%22">Hofmann P</searchLink>; German Centre for Cardiovascular Research, Institute of Medical Genetics, Carl von Ossietzky University, 26129 Oldenburg, Germany.<br /><searchLink fieldCode="AU" term="%22Hitz+MP%22">Hitz MP</searchLink>; German Centre for Cardiovascular Research, Institute of Medical Genetics, Carl von Ossietzky University, 26129 Oldenburg, Germany.<br /><searchLink fieldCode="AU" term="%22Schapiro+D%22">Schapiro D</searchLink>; Institute for Computational Biomedicine, Faculty of Medicine, University Hospital Heidelberg and Heidelberg University, 69120 Heidelberg, Germany.<br /><searchLink fieldCode="AU" term="%22Leclerc+S%22">Leclerc S</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.; Centre Hospitalier de I'Université de Montreal (CHUM) Research Centre, OPTILAB Diagnostic Laboratory, Montreal, QC H2X 0C1, Canada.<br /><searchLink fieldCode="AU" term="%22van+Vliet+PP%22">van Vliet PP</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.<br /><searchLink fieldCode="AU" term="%22Andelfinger+G%22">Andelfinger G</searchLink>; Cardiovascular Genetics, Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.
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  Data: <searchLink fieldCode="MM" term="%22Single-Cell+Analysis%22">Single-Cell Analysis*</searchLink>/<searchLink fieldCode="MM" term="%22Single-Cell+Analysis+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Heart%22">Heart*</searchLink>/<searchLink fieldCode="MM" term="%22Heart+embryology%22">embryology</searchLink> <br /><searchLink fieldCode="MM" term="%22Heart%22">Heart*</searchLink>/<searchLink fieldCode="MM" term="%22Heart+growth+%26+development%22">growth & development</searchLink> <br /><searchLink fieldCode="MM" term="%22Myocardium%22">Myocardium*</searchLink>/<searchLink fieldCode="MM" term="%22Myocardium+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Gene+Expression+Regulation%2C+Developmental%22">Gene Expression Regulation, Developmental*</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcription%2C+Genetic%22">Transcription, Genetic*</searchLink><br /><searchLink fieldCode="MH" term="%22RNA%2C+Long+Noncoding%22">RNA, Long Noncoding</searchLink>/<searchLink fieldCode="MH" term="%22RNA%2C+Long+Noncoding+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Endothelial+Cells%22">Endothelial Cells</searchLink>/<searchLink fieldCode="MH" term="%22Endothelial+Cells+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Induced+Pluripotent+Stem+Cells%22">Induced Pluripotent Stem Cells</searchLink>/<searchLink fieldCode="MH" term="%22Induced+Pluripotent+Stem+Cells+cytology%22">cytology</searchLink> ; <searchLink fieldCode="MH" term="%22Induced+Pluripotent+Stem+Cells%22">Induced Pluripotent Stem Cells</searchLink>/<searchLink fieldCode="MH" term="%22Induced+Pluripotent+Stem+Cells+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Computational+Biology%22">Computational Biology</searchLink>/<searchLink fieldCode="MH" term="%22Computational+Biology+methods%22">methods</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Single-Cell+Gene+Expression+Analysis%22">Single-Cell Gene Expression Analysis</searchLink> ; <searchLink fieldCode="MH" term="%22Gene+Expression+Profiling%22">Gene Expression Profiling</searchLink> ; <searchLink fieldCode="MH" term="%22Transcriptome%22">Transcriptome</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Heart maturation and remodelling during the foetal and early postnatal period are critical for the proper survival and growth of the foetus, yet our knowledge of the molecular processes involved is lacking for many cardiac cell types. To gain a deeper understanding of the transcriptional dynamics of the heart during the perinatal period, we performed single-cell RNA sequencing on foetal and early postnatal mouse hearts to establish a catalogue of 49,769 single-cell transcriptomes and used this for bioinformatics analyses. Pseudotime analyses and RNAscope fluorescence in situ hybridisation showed that while lncRNA H19 expression decreased over time in multiple cardiac cell types, it remained stably expressed in endocardial and valve endothelial cells. To further investigate this in a human setting, we generated human induced pluripotent stem cell (hiPSC)-derived endothelial cells and used single-cell data to develop a sorting strategy to separate endocardial from vascular endothelial cells, ensuring endothelial subtype purity. Knockdown of H19 in hiPSC-derived endocardial cells resulted in morphological changes, decreased expression of endothelial markers, and increased expression of mesenchymal markers, consistent with the onset of endothelial-to-mesenchymal transition. Together, our data suggest a role for H19 in maintaining endocardial and valve endothelial cell states during perinatal heart maturation.<br /> (© 2026. Published by The Company of Biologists.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Competing interests The authors declare no competing or financial interests.
– Name: Ref
  Label: References
  Group: RefInfo
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– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: G-17-0019170 Heart and Stroke Foundation of Canada; MIBAVA-Leducq 12CVD03 Fondation Leducq; Nationale Bank van België; 453653 Canada CAPMC CIHR; 27335 Fonds de Recherche du Québec - Sante; Deutsche Forschungsgemeinschaft; BMBF 01ZZ2004 German Federal Ministry of Education and Research
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  Data: <i>Keywords: </i>Endocardial development; H19; Heart maturation; Perinatal; Single-cell RNA-seq; Valve development
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        Text: English
    Subjects:
      – SubjectFull: RNA, Long Noncoding genetics
        Type: general
      – SubjectFull: Endothelial Cells metabolism
        Type: general
      – SubjectFull: Induced Pluripotent Stem Cells cytology
        Type: general
      – SubjectFull: Induced Pluripotent Stem Cells metabolism
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      – SubjectFull: Animals
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Single-Cell Gene Expression Analysis
        Type: general
      – SubjectFull: Gene Expression Profiling
        Type: general
      – SubjectFull: Transcriptome
        Type: general
      – SubjectFull: Single-Cell Analysis methods
        Type: general
      – SubjectFull: Heart embryology
        Type: general
      – SubjectFull: Heart growth & development
        Type: general
      – SubjectFull: Myocardium metabolism
        Type: general
      – SubjectFull: Gene Expression Regulation, Developmental
        Type: general
      – SubjectFull: Transcription, Genetic
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      – TitleFull: Transcriptional dynamics of the murine heart during perinatal development at single-cell resolution.
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            – D: 15
              M: 09
              Text: 2026 Sep 15
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          Numbering:
            – Type: volume
              Value: 15
            – Type: issue
              Value: 9
          Titles:
            – TitleFull: Biology open
              Type: main
ResultId 1