Foundry120 atlas

← IBD single-cell transcriptomics

IPF Cell Atlas

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Dataset overview

Participants 78
Samples 78
Reuse readiness 7.1/10 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
Illumina HiSeq 4000
Age group
adult
Disease groups
—
Anatomical sites
lung

Data availability

  • Raw counts

File types MTXRDSTXT

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Raw counts are advertised
  • Cell metadata are advertised
  • Participant mapping is available
  • Participant counts are documented

Limitations

  • Not documented: processed matrices are advertised
Extraction evidence & provenance

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

Assay

FieldValueEvidence
assay.assay_type single-cell RNA sequencing
Single Cell RNAseq of Whole Lung Dissociates from IPF, COPD and control lungs

Section geo_family_soft, offset —
assay.library_chemistry 10X Genomics 3 prime v2
10X Genomics 3 prime v2

Section sample_values_with_sample_counts.extract_protocol, offset —
assay.platform Illumina HiSeq 4000
Illumina HiSeq 4000

Section sample metadata, offset —
assay.reference_genome GRCh38 Release 91
Genome_build: GRCh38 Release 91

Section sample_values_with_sample_counts.data_processing, offset —
assay.sequencing_type scrna_seq
Single Cell RNAseq of Whole Lung Dissociates from IPF, COPD and control lungs

Section dataset summary, offset —

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 —

Data_Assets

FieldValueEvidence
data_assets.cell_metadata True
GSE136831_AllCells.Samples.CellType.MetadataTable.txt.gz

Section filelist.txt, offset —
data_assets.open_access True
"isOpenAccess": "Y"

Section europepmc_record, offset —
data_assets.participant_metadata True
including subject and library source, disease status and cell-type identities

Section geo_family_soft, offset —
data_assets.raw_counts True
GSE136831_RawCounts_Sparse.mtx.gz

Section filelist.txt, offset —
data_assets.raw_reads True
GSE136831_RAW.tar

Section geo_document, offset —

Processing

FieldValueEvidence
processing.cell_type_annotation_method study-assigned cell-type identities
cell-type identities we assigned in our study

Section data processing, offset —
processing.quality_control_reported True
Cells filtered with > 12% of transcriptome from intron-spanning reads; < 20% mitochondrial origin; at least 1000 unique genes

Section sample_values_with_sample_counts.data_processing, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['lung']
Whole Lung Dissociate

Section geo_family_soft, offset —
specimens.number_of_cells 312928
RawCounts_sparse.mtx.gz: ... 312,928 cells x 45,947 genes

Section sample_values_with_sample_counts.data_processing, offset —
specimens.number_of_samples 78
"sample_count": 78

Section sample_count, offset —
specimens.participant_to_sample_mapping_available True
Cell_MetaData.txt: MetaData to describe all 312,928 cells; including subject and library source

Section geo_family_soft, offset —