Single-cell RNA sequencing reveals that lung mesenchymal progenitor cells in IPF exhibit pathological features early in their differentiation trajectory.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 07 2020
07 07 2020
Historique:
received:
03
12
2019
accepted:
06
05
2020
entrez:
9
7
2020
pubmed:
9
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
In Idiopathic Pulmonary Fibrosis (IPF), there is unrelenting scarring of the lung mediated by pathological mesenchymal progenitor cells (MPCs) that manifest autonomous fibrogenicity in xenograft models. To determine where along their differentiation trajectory IPF MPCs acquire fibrogenic properties, we analyzed the transcriptome of 335 MPCs isolated from the lungs of 3 control and 3 IPF patients at the single-cell level. Using transcriptional entropy as a metric for differentiated state, we found that the least differentiated IPF MPCs displayed the largest differences in their transcriptional profile compared to control MPCs. To validate entropy as a surrogate for differentiated state functionally, we identified increased CD44 as a characteristic of the most entropic IPF MPCs. Using FACS to stratify IPF MPCs based on CD44 expression, we determined that CD44
Identifiants
pubmed: 32636398
doi: 10.1038/s41598-020-66630-5
pii: 10.1038/s41598-020-66630-5
pmc: PMC7341888
doi:
Substances chimiques
Hyaluronan Receptors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
11162Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL146501
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002494
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125236
Pays : United States
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