Developmental origins of cell heterogeneity in the human lung


Journal article


A. Sountoulidis, Sergio Marco Salas, Emelie Braun, Christophe Avenel, J. Bergenstråhle, Marco Vicari, Paulo Czarnewski, Jonas Theelke, A. Liontos, X. Abalo, Žaneta Andrusivová, Michaela Asp, Xiaofei Li, L. Hu, Sanem Sariyar, Anna Martinez Casals, B. Ayoglu, A. Firsova, J. Michaëlsson, E. Lundberg, C. Wählby, E. Sundström, S. Linnarsson, J. Lundeberg, M. Nilsson, C. Samakovlis
bioRxiv, 2022

Semantic Scholar DOI
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APA   Click to copy
Sountoulidis, A., Salas, S. M., Braun, E., Avenel, C., Bergenstråhle, J., Vicari, M., … Samakovlis, C. (2022). Developmental origins of cell heterogeneity in the human lung. BioRxiv.


Chicago/Turabian   Click to copy
Sountoulidis, A., Sergio Marco Salas, Emelie Braun, Christophe Avenel, J. Bergenstråhle, Marco Vicari, Paulo Czarnewski, et al. “Developmental Origins of Cell Heterogeneity in the Human Lung.” bioRxiv (2022).


MLA   Click to copy
Sountoulidis, A., et al. “Developmental Origins of Cell Heterogeneity in the Human Lung.” BioRxiv, 2022.


BibTeX   Click to copy

@article{a2022a,
  title = {Developmental origins of cell heterogeneity in the human lung},
  year = {2022},
  journal = {bioRxiv},
  author = {Sountoulidis, A. and Salas, Sergio Marco and Braun, Emelie and Avenel, Christophe and Bergenstråhle, J. and Vicari, Marco and Czarnewski, Paulo and Theelke, Jonas and Liontos, A. and Abalo, X. and Andrusivová, Žaneta and Asp, Michaela and Li, Xiaofei and Hu, L. and Sariyar, Sanem and Casals, Anna Martinez and Ayoglu, B. and Firsova, A. and Michaëlsson, J. and Lundberg, E. and Wählby, C. and Sundström, E. and Linnarsson, S. and Lundeberg, J. and Nilsson, M. and Samakovlis, C.}
}

Abstract

The lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.


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