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Ciliated (FOXJ1+) Cells Display Reduced Ferritin Light Chain in the Airways of Idiopathic Pulmonary Fibrosis Patients

Wijk, Sofia C. LU ; Prabhala, Pavan LU ; Löfdahl, Anna LU ; Nybom, Annika LU ; Lang, Stefan LU orcid ; Brunnström, Hans LU orcid ; Bjermer, Leif LU ; Westergren-Thorsson, Gunilla LU orcid and Magnusson, Mattias LU (2022) In Cells 11(6).
Abstract

Cell-based therapies hold great promise in re-establishing organ function for many diseases, including untreatable lung diseases such as idiopathic pulmonary fibrosis (IPF). However, many hurdles still remain, in part due to our lack of knowledge about the disease-driving mechanisms that may affect the cellular niche and thereby possibly hinder the function of any transplanted cells by imposing the disease phenotype onto the newly generated progeny. Recent findings have demonstrated increased ciliation of lung cells from IPF patients, but how this affects ciliated cell function and the airway milieu is not well-known. Here, we performed single-cell RNA sequencing on primary ciliated (FOJ1+) cells isolated from IPF patients... (More)

Cell-based therapies hold great promise in re-establishing organ function for many diseases, including untreatable lung diseases such as idiopathic pulmonary fibrosis (IPF). However, many hurdles still remain, in part due to our lack of knowledge about the disease-driving mechanisms that may affect the cellular niche and thereby possibly hinder the function of any transplanted cells by imposing the disease phenotype onto the newly generated progeny. Recent findings have demonstrated increased ciliation of lung cells from IPF patients, but how this affects ciliated cell function and the airway milieu is not well-known. Here, we performed single-cell RNA sequencing on primary ciliated (FOJ1+) cells isolated from IPF patients and from healthy control donors. The sequencing identified multiple biological processes, such as cilium morphogenesis and cell signaling, that were significantly changed between IPF and healthy ciliated cells. Ferritin light chain (FTL) was downregulated in IPF, which suggests that iron metabolism may be affected in the IPF ciliated cells. The RNA expression was confirmed at the protein level with histological localization in lung tissue, prompting future functional assays to reveal the potential role of FTL. Taken together, our data demonstrate the importance of careful analyses in pure cell populations to better understand the IPF disease mechanism.

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Please use this url to cite or link to this publication:
@article{4a42a82c-21d0-455a-af83-4d6398b5d78e,
  abstract     = {{<p>Cell-based therapies hold great promise in re-establishing organ function for many diseases, including untreatable lung diseases such as idiopathic pulmonary fibrosis (IPF). However, many hurdles still remain, in part due to our lack of knowledge about the disease-driving mechanisms that may affect the cellular niche and thereby possibly hinder the function of any transplanted cells by imposing the disease phenotype onto the newly generated progeny. Recent findings have demonstrated increased ciliation of lung cells from IPF patients, but how this affects ciliated cell function and the airway milieu is not well-known. Here, we performed single-cell RNA sequencing on primary ciliated (FOJ1<sup>+</sup>) cells isolated from IPF patients and from healthy control donors. The sequencing identified multiple biological processes, such as cilium morphogenesis and cell signaling, that were significantly changed between IPF and healthy ciliated cells. Ferritin light chain (FTL) was downregulated in IPF, which suggests that iron metabolism may be affected in the IPF ciliated cells. The RNA expression was confirmed at the protein level with histological localization in lung tissue, prompting future functional assays to reveal the potential role of FTL. Taken together, our data demonstrate the importance of careful analyses in pure cell populations to better understand the IPF disease mechanism.</p>}},
  author       = {{Wijk, Sofia C. and Prabhala, Pavan and Löfdahl, Anna and Nybom, Annika and Lang, Stefan and Brunnström, Hans and Bjermer, Leif and Westergren-Thorsson, Gunilla and Magnusson, Mattias}},
  issn         = {{2073-4409}},
  keywords     = {{Basal cells; Ciliated cells; Ferritin light chain; Immunofluorescence; IPF; Single-cell RNA sequencing; Stem cell therapy}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Ciliated (FOXJ1<sup>+</sup>) Cells Display Reduced Ferritin Light Chain in the Airways of Idiopathic Pulmonary Fibrosis Patients}},
  url          = {{http://dx.doi.org/10.3390/cells11061031}},
  doi          = {{10.3390/cells11061031}},
  volume       = {{11}},
  year         = {{2022}},
}