Human distal lung maps and lineage hierarchies reveal a bipotent progenitor.

Autor: Kadur Lakshminarasimha Murthy P; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA., Sontake V; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA., Tata A; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA., Kobayashi Y; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA.; Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan., Macadlo L; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA., Okuda K; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Conchola AS; Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA., Nakano S; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Gregory S; Department of Neurology, Duke University Medical Center, Durham, NC, USA., Miller LA; California National Primate Research Center, Davis, CA, USA.; Department of Anatomy, Physiology and Cell biology, School of Veterinary Medicine, University of California, Davis, CA, USA., Spence JR; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA., Engelhardt JF; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; Department of Anatomy & Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Boucher RC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Rock JR; Department of Immunology Discovery, Genentech, South San Francisco, CA, USA., Randell SH; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Tata PR; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA. purushothamarao.tata@duke.edu.; Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA. purushothamarao.tata@duke.edu.; Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USA. purushothamarao.tata@duke.edu.; Division of Pulmonary Critical Care, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. purushothamarao.tata@duke.edu.; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA. purushothamarao.tata@duke.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Apr; Vol. 604 (7904), pp. 111-119. Date of Electronic Publication: 2022 Mar 30.
DOI: 10.1038/s41586-022-04541-3
Abstrakt: 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 1-4 . 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 5-7 . 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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