GEO series

WI-38 cell line as model for myofibroblast and lipofibroblast switch

GSE264038 Homo sapiens (human) Single-cell RNA-seq 12 samples Submitted 2024/07/03 Platform GPL24676

At a glance

Single-cell RNA-seq · human · 12 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Homo sapiens (human)
Samples: 12 samples: 4 × WI-38 TGFB1 vs 3 × WI-38 control vs 3 × WI-38 MET vs 2 × WI-38 TGFB1- METGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Highlighting fibroblast plasticity in lung fibrosis: the WI-38 cell line as a model for investigating the myofibroblast and lipofibroblast switchTheranostics · 2024

Summary (written by the submitters)

Background: Myofibroblasts (MYFs) are generally considered the principal culprits in excessive extracellular matrix deposition and scar formation in the pathogenesis of lung fibrosis. Lipofibroblasts (LIFs), on the other hand, are defined by their lipid-storing capacity and are predominantly found in the alveolar regions of the lung. They have been proposed to play a protective role in lung fibrosis.

Read the full summary ↓

We previously reported that a LIF to MYF reversible differentiation switch occurred during fibrosis formation and resolution. In this study, we tested whether WI-38 cells, a human embryonic lung fibroblast cell line, could be used to study fibroblast differentiation towards the LIF or MYF phenotype and whether this could be relevant for idiopathic pulmonary fibrosis (IPF). Methods: using WI-38 cells, MYF differentiation was triggered using TGF-β1 treatment and LIF differentiation using Metformin treatment. We analyzed the LIF to MYF and MYF to LIF differentiation by pre-treating the WI-38 cells with TGF-β1 or Metformin first, followed by treatment with Metformin and TGF-β1, respectively. We used IF, qPCR and bulk RNA-Seq to analyze the phenotypic and transcriptomic changes in the cells. We correlated our in vitro transcriptome data from WI-38 cells (obtained via bulk RNA sequencing) with the transcriptomic signature of LIFs and MYFs derived from the IPF cell atlas as well as with our own single-cell transcriptomic data from IFP patients-derived lung fibroblasts (LF-IPF) cultured in vitro. We also carried out alveolosphere assays to evaluate the ability of the proposed LIF and MYF cells to support the growth of alveolar epithelial type 2 cells. Results: WI-38 and LF-IPF display similar phenotypical and gene expression responses to TGF-β1 and Metformin treatment. Bulk RNA-Seq analysis of WI-38 and LF-IPF treated with TGF-β1, or Metformin indicate similar transcriptomic changes. We also show the partial conservation of the LIF and MYF signature extracted from the Habermann et al. scRNA-seq dataset in WI-38 cells treated with Metformin or TGF-β1, respectively. Alveolosphere assays indicate that LIFs enhance organoid growth, while MYFs inhibit organoid growth. Finally, we provide evidence supporting the LIF to MYF reversible switch using WI-38 cells. Conclusions: WI-38 cells represent a versatile and reliable model to study the intricate dynamics of fibroblast differentiation towards the MYF or LIF phenotype associated with lung fibrosis formation and resolution, providing valuable insights to drive future research

Published in

Highlighting fibroblast plasticity in lung fibrosis: the WI-38 cell line as a model for investigating the myofibroblast and lipofibroblast switch

Vásquez-Pacheco E, Marega M, Lingampally A et al. · Theranostics 2024 · PMID 38948058 · doi:10.7150/thno.93519

This dataset

Open GSE264038 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE264038_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1100584 and SRA study SRP501912. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38948058) ↗

Study design

4 × WI-38 TGFB1 vs 3 × WI-38 control vs 3 × WI-38 MET vs 2 × WI-38 TGFB1- MET

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8209083 WI-38 control 1 WI-38 control
GSM8209084 WI-38 control 2 WI-38 control
GSM8209085 WI-38 control 3 WI-38 control
GSM8209086 WI-38 MET 1 WI-38 MET
GSM8209087 WI-38 MET 2 WI-38 MET
GSM8209088 WI-38 MET 3 WI-38 MET
GSM8209089 WI-38 TGFB1 1 WI-38 TGFB1
GSM8209090 WI-38 TGFB1 2 WI-38 TGFB1
GSM8209091 WI-38 TGFB1- 1 WI-38 TGFB1
GSM8209092 WI-38 TGFB1- 2 WI-38 TGFB1
GSM8209093 WI-38 TGFB1- MET 1 WI-38 TGFB1- MET
GSM8209094 WI-38 TGFB1- MET 2 WI-38 TGFB1- MET

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