Early lineage specification defines alveolar epithelial ontogeny in the murine lung.

Animals Cell Differentiation Cell Lineage Female In Situ Hybridization, Fluorescence Lung / cytology Mice Pregnancy Pulmonary Alveoli / cytology Transcriptome
alveolar epithelium lineage fate lung development single-cell RNA sequencing

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
05 03 2019
Historique:
pubmed: 21 2 2019
medline: 9 4 2020
entrez: 21 2 2019
Statut: ppublish

Résumé

During the stepwise specification and differentiation of tissue-specific multipotent progenitors, lineage-specific transcriptional networks are activated or repressed to orchestrate cell specification. The gas-exchange niche in the lung contains two major epithelial cell types, alveolar type 1 (AT1) and AT2 cells, and the timing of lineage specification of these cells is critical for the correct formation of this niche and postnatal survival. Integrating cell-specific lineage tracing studies, spatially specific mRNA transcript and protein expression, and single-cell RNA-sequencing analysis, we demonstrate that specification of alveolar epithelial cell fate begins concomitantly with the proximal-distal specification of epithelial progenitors and branching morphogenesis earlier than previously appreciated. By using a newly developed dual-lineage tracing system, we show that bipotent alveolar cells that give rise to AT1 and AT2 cells are a minor contributor to the alveolar epithelial population. Furthermore, single-cell assessment of the transcriptome identifies specified AT1 and AT2 progenitors rather than bipotent cells during sacculation. These data reveal a paradigm of organ formation whereby lineage specification occurs during the nascent stages of development coincident with broad tissue-patterning processes, including axial patterning of the endoderm and branching morphogenesis.

Identifiants

DOI: 10.1073/pnas.1813952116 PMID: 30782824 PMC: PMC6410851
pubmed: 30782824
pii: 1813952116
doi: 10.1073/pnas.1813952116
pmc: PMC6410851
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

4362-4371

Subventions

Organisme : NHLBI NIH HHS
ID : F31 HL140785
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007586
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132349
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007915
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL134745
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL110942
Pays : United States
Organisme : NHLBI NIH HHS
ID : DP2 HL147123
Pays : United States
Organisme : NHLBI NIH HHS
ID : L40 HL129325
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD043245
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007843
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL140129
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132999
Pays : United States

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

David B Frank (DB)

Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104; frankd@email.chop.edu jainr@pennmedicine.upenn.edu emorrise@pennmedicine.upenn.edu.
Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.

Ian J Penkala (IJ)

Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Jarod A Zepp (JA)

Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Aravind Sivakumar (A)

Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104.
Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.

Ricardo Linares-Saldana (R)

Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

William J Zacharias (WJ)

Division of Pulmonary Biology, Department of Pediatrics, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, OH 45229.

Katharine G Stolz (KG)

Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104.

Josh Pankin (J)

Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104.
Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104.

MinQi Lu (M)

Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104.

Qiaohong Wang (Q)

Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Apoorva Babu (A)

Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Li Li (L)

Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.

Su Zhou (S)

Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.

Michael P Morley (MP)

Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Rajan Jain (R)

Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104; frankd@email.chop.edu jainr@pennmedicine.upenn.edu emorrise@pennmedicine.upenn.edu.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Edward E Morrisey (EE)

Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104; frankd@email.chop.edu jainr@pennmedicine.upenn.edu emorrise@pennmedicine.upenn.edu.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Early lineage specification defines alveolar...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Early lineage specification defines alveolar...
Recherchemedicale.com › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Développement embryonnaire et foetal › Développement embryonnaire › Lignage cellulaire › Early lineage specification defines alveolar...
Recherchemedicale.com › Techniques d'investigation › Techniques génétiques › Hybridation in situ › Hybridation fluorescente in situ › Early lineage specification defines alveolar...
Recherchemedicale.com › Appareil respiratoire › Poumon › Early lineage specification defines alveolar...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Early lineage specification defines alveolar...
Recherchemedicale.com › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Early lineage specification defines alveolar...
Recherchemedicale.com › Appareil respiratoire › Poumon › Alvéoles pulmonaires › Early lineage specification defines alveolar...
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Transcriptome › Early lineage specification defines alveolar...