A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Michaela Asp - , KTH Royal Institute of Technology (Author)
  • Stefania Giacomello - , Stockholm University (Author)
  • Ludvig Larsson - , KTH Royal Institute of Technology (Author)
  • Chenglin Wu - , Stockholm University (Author)
  • Daniel Fürth - , Cold Spring Harbor Laboratory (Author)
  • Xiaoyan Qian - , Stockholm University (Author)
  • Eva Wärdell - , Karolinska Institutet (Author)
  • Joaquin Custodio - , Karolinska Institutet (Author)
  • Johan Reimegård - , Uppsala University (Author)
  • Fredrik Salmén - , Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht (Author)
  • Cecilia Österholm - , Karolinska Institutet (Author)
  • Patrik L Ståhl - , KTH Royal Institute of Technology (Author)
  • Erik Sundström - , Karolinska Institutet (Author)
  • Elisabet Åkesson - , Karolinska Institutet (Author)
  • Olaf Bergmann - , Dynamics and Mechanisms of Cell Renewal (Junior Research Group), Karolinska Institutet (Author)
  • Magda Bienko - , Karolinska Institutet (Author)
  • Agneta Månsson-Broberg - , Karolinska Institutet (Author)
  • Mats Nilsson - , Stockholm University (Author)
  • Christer Sylvén - , Karolinska Institutet (Author)
  • Joakim Lundeberg - , KTH Royal Institute of Technology (Author)

Abstract

The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.

Details

Original languageEnglish
Pages (from-to)1647-1660.e19
JournalCell
Volume179
Issue number7
Publication statusPublished - 12 Dec 2019
Peer-reviewedYes

External IDs

Scopus 85076165520

Keywords

Keywords

  • Female, Gene Expression Regulation, Developmental, Heart/embryology, Humans, Male, Morphogenesis, Myocytes, Cardiac/cytology, RNA-Seq, Single-Cell Analysis, Transcriptome