Journal article
Human distal lung maps and lineage hierarchies reveal a bipotent progenitor
Nature (London), Vol.604(7904), pp.111-119
04/2022
DOI: 10.1038/s41586-022-04541-3
PMCID: PMC9169066
PMID: 35355018
Abstract
Mapping the spatial distribution and molecular identity of constituent cells is essential for understanding tissue dynamics in health and disease. We lack a comprehensive map of human distal airways, including the terminal and respiratory bronchioles (TRBs), which are implicated in respiratory diseases
. Here, using spatial transcriptomics and single-cell profiling of microdissected distal airways, we identify molecularly distinct TRB cell types that have not-to our knowledge-been previously characterized. These include airway-associated LGR5
fibroblasts and TRB-specific alveolar type-0 (AT0) cells and TRB secretory cells (TRB-SCs). Connectome maps and organoid-based co-cultures reveal that LGR5
fibroblasts form a signalling hub in the airway niche. AT0 cells and TRB-SCs are conserved in primates and emerge dynamically during human lung development. Using a non-human primate model of lung injury, together with human organoids and tissue specimens, we show that alveolar type-2 cells in regenerating lungs transiently acquire an AT0 state from which they can differentiate into either alveolar type-1 cells or TRB-SCs. This differentiation programme is distinct from that identified in the mouse lung
. Our study also reveals mechanisms that drive the differentiation of the bipotent AT0 cell state into normal or pathological states. In sum, our findings revise human lung cell maps and lineage trajectories, and implicate an epithelial transitional state in primate lung regeneration and disease.
Details
- Title: Subtitle
- Human distal lung maps and lineage hierarchies reveal a bipotent progenitor
- Creators
- Preetish Kadur Lakshminarasimha Murthy - Duke University School of MedicineVishwaraj Sontake - Duke UniversityAleksandra Tata - Duke UniversityYoshihiko Kobayashi - Duke UniversityLauren Macadlo - Duke UniversityKenichi Okuda - University of North Carolina at Chapel HillAnsley S Conchola - University of MichiganSatoko Nakano - University of North Carolina at Chapel HillSimon Gregory - Duke University Medical CenterLisa A Miller - University of California, DavisJason R Spence - University of MichiganJohn F Engelhardt - University of IowaRichard C Boucher - University of North Carolina at Chapel HillJason R Rock - GenentechScott H Randell - University of North Carolina at Chapel HillPurushothama Rao Tata - Duke University
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.604(7904), pp.111-119
- DOI
- 10.1038/s41586-022-04541-3
- PMID
- 35355018
- PMCID
- PMC9169066
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- R24 HD000836 / NICHD NIH HHS R01 HL127002 / NHLBI NIH HHS R01 HL119215 / NHLBI NIH HHS U01 HL134766 / NHLBI NIH HHS P30 CA014236 / NCI NIH HHS R01 HL153375 / NHLBI NIH HHS R00 HL127181 / NHLBI NIH HHS R01 HL146557 / NHLBI NIH HHS P30 DK065988 / NIDDK NIH HHS
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284357602771
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