Foundry120 atlas

← IBD single-cell transcriptomics

IPF Cell Atlas

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Dataset overview

Participants 78
Samples None
Reuse readiness 2.3/10 evidence-backed score

miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly.

Wildung M, Herr C, Riedel D, Wiedwald C, Moiseenko A, Ramírez F, Tasena H, Heimerl M, et al. · International journal of molecular sciences · 2022

Abstract

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (<i>miR449)</i>. In vitro, <i>miR449</i> was strongly increased during airway epithelial mucociliary differentiation. In vivo, <i>miR449</i> was upregulated during recovery from chemical or infective insults. <i>miR0449</i><sup>-/-</sup> mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and <i>Haemophilus influenzae</i> exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged <i>miR449<sup>-/-</sup></i> mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in <i>miR449</i>-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon <i>miR449</i> overexpression in vitro and upregulated in <i>miR449<sup>-/-</sup></i> mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in <i>miR449<sup>-/-</sup></i> cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between <i>miR449</i>, ciliary dysfunction, and COPD pathogenesis.

doi:10.3390/ijms23147749 ↗ PMID 35887096 ↗ PMC9320302 ↗

Study facts

Organism
Homo sapiens
Platform
—
Age group
adult
Disease groups
—
Anatomical sites
—

Data availability

Specific data assets have not been resolved from the source yet — see the source repository below for the full file listing.

File types MTXRDSTXT

Strengths & limitations for reuse

Strengths

  • Participant counts are documented

Limitations

  • Not documented: raw counts are advertised
  • Not documented: processed matrices are advertised
  • Not documented: cell metadata are advertised
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Cohort

FieldValueEvidence
cohort.age_group adult from source
GEO age characteristics: 32; 21; 49; 29; 32; 50; 41; 56; 37; 80; 23; 65; 64; 29; 66; 66; 61; 62; 35; 22; 25; 67; 48; 66; 31; 20; 54; 46; 57; 62; 58; 55; 66; 66; 63; 59; 60; 70; 66; 61; 57; 66; 65; 62; 57; 73; 68; 59; 56; 67; 66; 63; 67; 70; 65; 71; 69; 67; 59; 70; 56; 61; 62; 65; 78; 69; 67; 59; 70; 64; 66; 60; 66; 68; 54;

Section GEO family SOFT, offset —
cohort.non_ibd_controls 28
profiling 312,928 cells from 32 IPF, 28 smoker and nonsmoker controls, and 18 chronic obstructive pulmonary disease (COPD) lungs

Section abstract, offset —
cohort.total_participants 78
profiling 312,928 cells from 32 IPF, 28 smoker and nonsmoker controls, and 18 chronic obstructive pulmonary disease (COPD) lungs

Section abstract, offset —