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Sci Adv. 2019 Dec 4;5(12):eaaw3851. doi: 10.1126/sciadv.aaw3851. eCollection 2019 Dec.

Single-cell connectomic analysis of adult mammalian lungs.

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
2
Vascular Biology and Therapeutics, Yale University, New Haven, CT 06520, USA.
3
Medical Scientist Training Program, Yale School of Medicine, New Haven, CT 06510, USA.
4
Section of Pulmonary, Critical Care and Sleep Medicine, Yale University, New Haven, CT 06520, USA.
5
Yale Systems Biology Institute, Yale University, West Haven, CT 06516, USA.
6
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
7
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
8
Department of Anesthesiology, Yale University, New Haven, CT 06510, USA.
9
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA.
10
Applied Mathematics Program, Yale University, New Haven, CT 06511, USA.
11
Thoracic Surgery, Yale School of Medicine, New Haven, CT 06510, USA.
12
Department of Pathology, Yale University, New Haven, CT 06520, USA.

Abstract

Efforts to decipher chronic lung disease and to reconstitute functional lung tissue through regenerative medicine have been hampered by an incomplete understanding of cell-cell interactions governing tissue homeostasis. Because the structure of mammalian lungs is highly conserved at the histologic level, we hypothesized that there are evolutionarily conserved homeostatic mechanisms that keep the fine architecture of the lung in balance. We have leveraged single-cell RNA sequencing techniques to identify conserved patterns of cell-cell cross-talk in adult mammalian lungs, analyzing mouse, rat, pig, and human pulmonary tissues. Specific stereotyped functional roles for each cell type in the distal lung are observed, with alveolar type I cells having a major role in the regulation of tissue homeostasis. This paper provides a systems-level portrait of signaling between alveolar cell populations. These methods may be applicable to other organs, providing a roadmap for identifying key pathways governing pathophysiology and informing regenerative efforts.

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