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| Status |
Public on Nov 14, 2023 |
| Title |
Autocrine Sfrp1 inhibits lung fibroblast invasion during transition to injury induced myofibroblasts |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Several distinct lineages of fibroblasts support homeostatic tissue niche functions, yet, specific activation states and phenotypic trajectories of fibroblasts during injury repair have remained unclear. Here, we combined spatial transcriptomics, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1+ cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1+ transitional fibroblasts and Cthrc1+ myofibroblasts. Tgfβ1 downregulated Sfrp1 in non-invasive transitional cells and induced their switch to an invasive Cthrc1+ myofibroblast identity. Finally, using loss of function experiments we show that autocrine Sfrp1 directly inhibits fibroblast invasion by regulating the RhoA pathway. In summary, our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies Sfrp1 as an autocrine inhibitor of fibroblast invasion during early stages of fibrogenesis.
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| Overall design |
We performed gene expression microarray analysis in primary human pulmonary fibroblasts treated with Sfrp1-siRNA and controls
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| Contributor(s) |
Mayr CH, Sengupta A, Ansari M, Pestoni JC, Ogar P, Angelidis I, Liontos A, Rodriguez-Castillo A, Lang N, Strunz M, Asgharpour S, Porras-Gonzalez DL, Oehrle B, Viteri-Alvarez V, Fernandez IE, Irmler M, Beckers J, Eickelberg O, Stoleriu MG, Kneidinger N, Yildirim AO, Ahlbrecht K, Morty RE, Samakovlis C, Theis FJ, Burgstaller G, Schiller HB |
| Citation(s) |
38212077 |
| Submission date |
Jul 06, 2022 |
| Last update date |
Feb 15, 2024 |
| Contact name |
Johannes Beckers |
| E-mail(s) |
johannes.beckers@helmholtz-munich.de
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| Organization name |
Helmholtz Zentrum Muenchen
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| Department |
Institute of Experimental Genetics
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| Street address |
Ingolstaedter Landstr. 1
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| City |
Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (9)
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| GSM6297263 |
Primary_lung_fibroblasts_control_siRNA_rep1 |
| GSM6297264 |
Primary_lung_fibroblasts_control_siRNA_rep2 |
| GSM6297265 |
Primary_lung_fibroblasts_control_siRNA_rep3 |
| GSM6297266 |
Primary_lung_fibroblasts_Sfrp1_siRNA_rep1 |
| GSM6297267 |
Primary_lung_fibroblasts_Sfrp1_siRNA_rep2 |
| GSM6297268 |
Primary_lung_fibroblasts_Sfrp1_siRNA_rep3 |
| GSM6297269 |
Primary_lung_fibroblasts_untreated_rep1 |
| GSM6297270 |
Primary_lung_fibroblasts_untreated_rep2 |
| GSM6297271 |
Primary_lung_fibroblasts_untreated_rep3 |
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| Relations |
| BioProject |
PRJNA856233 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE207561_RAW.tar |
9.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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