Publication

TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation

Ng-Blichfeldt, J-P., de Jong, T., Kortekaas, R. K., Wu, X., Lindner, M., Guryev, V., Hiemstra, P. S., Stolk, J., Koenigshoff, M. & Gosens, R., Jul-2019, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 317, 1, p. L14-L28 15 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Ng-Blichfeldt, J-P., de Jong, T., Kortekaas, R. K., Wu, X., Lindner, M., Guryev, V., ... Gosens, R. (2019). TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation. American Journal of Physiology - Lung Cellular and Molecular Physiology, 317(1), L14-L28. https://doi.org/10.1152/ajplung.00400.2018

Author

Ng-Blichfeldt, John-Poul ; de Jong, Tristan ; Kortekaas, Rosa K. ; Wu, Xinhui ; Lindner, Michael ; Guryev, Victor ; Hiemstra, Pieter S. ; Stolk, Jan ; Koenigshoff, Melanie ; Gosens, Reinoud. / TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2019 ; Vol. 317, No. 1. pp. L14-L28.

Harvard

Ng-Blichfeldt, J-P, de Jong, T, Kortekaas, RK, Wu, X, Lindner, M, Guryev, V, Hiemstra, PS, Stolk, J, Koenigshoff, M & Gosens, R 2019, 'TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 317, no. 1, pp. L14-L28. https://doi.org/10.1152/ajplung.00400.2018

Standard

TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation. / Ng-Blichfeldt, John-Poul; de Jong, Tristan; Kortekaas, Rosa K.; Wu, Xinhui; Lindner, Michael; Guryev, Victor; Hiemstra, Pieter S.; Stolk, Jan; Koenigshoff, Melanie; Gosens, Reinoud.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 317, No. 1, 07.2019, p. L14-L28.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Ng-Blichfeldt J-P, de Jong T, Kortekaas RK, Wu X, Lindner M, Guryev V et al. TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2019 Jul;317(1):L14-L28. https://doi.org/10.1152/ajplung.00400.2018


BibTeX

@article{5f7d8373714347f0b9464daa3efa10ef,
title = "TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation",
abstract = "Transforming growth factor-β (TGF-β)-induced fibroblast-to-myofibroblast differentiation contributes to remodeling in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, but whether this impacts the ability of fibroblasts to support lung epithelial repair remains little explored. We pre-treated human lung fibroblasts (primary [phFB] or MRC5 cells) with recombinant human TGF-β to induce myofibroblast differentiation, then co-cultured them with adult mouse lung EpCAM+ cells to investigate their capacity to support epithelial organoid formation in vitro. While control phFB and MRC5 lung fibroblasts supported organoid formation of mouse EpCAM+ cells, TGF-β-pre-treatment of both phFB and MRC5 impaired organoid-supporting ability. We performed RNA sequencing of TGF-β treated phFB, which revealed altered expression of key Wnt signaling pathway components and Wnt/β-catenin target genes, and modulated expression of secreted factors involved in mesenchymal-epithelial signaling. TGF-β profoundly skewed the transcriptional program induced by the Wnt/β-catenin activator CHIR99021 (CHIR). Supplementing organoid culture media recombinant hepatocyte growth factor (HGF) or fibroblast growth factor 7 (FGF7) promoted organoid formation when using TGF-β pre-treated fibroblasts. In conclusion, TGF-β-induced myofibroblast differentiation results in Wnt/β-catenin pathway skewing, and impairs fibroblast ability to support epithelial repair likely through multiple mechanisms including modulation of secreted growth factors.",
keywords = "lung regeneration/repair, lung stem cells, mesenchymal-epithelial signaling, TGF-beta, Wnt/beta-catenin signaling, HEPATOCYTE GROWTH-FACTOR, FACTOR SCATTER FACTOR, SELF-RENEWAL, STEM-CELLS, CROSS-TALK, REPAIR, REGENERATION, EXPRESSION, PATHWAY, PROLIFERATION",
author = "John-Poul Ng-Blichfeldt and {de Jong}, Tristan and Kortekaas, {Rosa K.} and Xinhui Wu and Michael Lindner and Victor Guryev and Hiemstra, {Pieter S.} and Jan Stolk and Melanie Koenigshoff and Reinoud Gosens",
year = "2019",
month = "7",
doi = "10.1152/ajplung.00400.2018",
language = "English",
volume = "317",
pages = "L14--L28",
journal = "American Journal of Physiology - Lung Cellular and Molecular Physiology",
issn = "1040-0605",
publisher = "AMER PHYSIOLOGICAL SOC",
number = "1",

}

RIS

TY - JOUR

T1 - TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation

AU - Ng-Blichfeldt, John-Poul

AU - de Jong, Tristan

AU - Kortekaas, Rosa K.

AU - Wu, Xinhui

AU - Lindner, Michael

AU - Guryev, Victor

AU - Hiemstra, Pieter S.

AU - Stolk, Jan

AU - Koenigshoff, Melanie

AU - Gosens, Reinoud

PY - 2019/7

Y1 - 2019/7

N2 - Transforming growth factor-β (TGF-β)-induced fibroblast-to-myofibroblast differentiation contributes to remodeling in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, but whether this impacts the ability of fibroblasts to support lung epithelial repair remains little explored. We pre-treated human lung fibroblasts (primary [phFB] or MRC5 cells) with recombinant human TGF-β to induce myofibroblast differentiation, then co-cultured them with adult mouse lung EpCAM+ cells to investigate their capacity to support epithelial organoid formation in vitro. While control phFB and MRC5 lung fibroblasts supported organoid formation of mouse EpCAM+ cells, TGF-β-pre-treatment of both phFB and MRC5 impaired organoid-supporting ability. We performed RNA sequencing of TGF-β treated phFB, which revealed altered expression of key Wnt signaling pathway components and Wnt/β-catenin target genes, and modulated expression of secreted factors involved in mesenchymal-epithelial signaling. TGF-β profoundly skewed the transcriptional program induced by the Wnt/β-catenin activator CHIR99021 (CHIR). Supplementing organoid culture media recombinant hepatocyte growth factor (HGF) or fibroblast growth factor 7 (FGF7) promoted organoid formation when using TGF-β pre-treated fibroblasts. In conclusion, TGF-β-induced myofibroblast differentiation results in Wnt/β-catenin pathway skewing, and impairs fibroblast ability to support epithelial repair likely through multiple mechanisms including modulation of secreted growth factors.

AB - Transforming growth factor-β (TGF-β)-induced fibroblast-to-myofibroblast differentiation contributes to remodeling in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, but whether this impacts the ability of fibroblasts to support lung epithelial repair remains little explored. We pre-treated human lung fibroblasts (primary [phFB] or MRC5 cells) with recombinant human TGF-β to induce myofibroblast differentiation, then co-cultured them with adult mouse lung EpCAM+ cells to investigate their capacity to support epithelial organoid formation in vitro. While control phFB and MRC5 lung fibroblasts supported organoid formation of mouse EpCAM+ cells, TGF-β-pre-treatment of both phFB and MRC5 impaired organoid-supporting ability. We performed RNA sequencing of TGF-β treated phFB, which revealed altered expression of key Wnt signaling pathway components and Wnt/β-catenin target genes, and modulated expression of secreted factors involved in mesenchymal-epithelial signaling. TGF-β profoundly skewed the transcriptional program induced by the Wnt/β-catenin activator CHIR99021 (CHIR). Supplementing organoid culture media recombinant hepatocyte growth factor (HGF) or fibroblast growth factor 7 (FGF7) promoted organoid formation when using TGF-β pre-treated fibroblasts. In conclusion, TGF-β-induced myofibroblast differentiation results in Wnt/β-catenin pathway skewing, and impairs fibroblast ability to support epithelial repair likely through multiple mechanisms including modulation of secreted growth factors.

KW - lung regeneration/repair

KW - lung stem cells

KW - mesenchymal-epithelial signaling

KW - TGF-beta

KW - Wnt/beta-catenin signaling

KW - HEPATOCYTE GROWTH-FACTOR

KW - FACTOR SCATTER FACTOR

KW - SELF-RENEWAL

KW - STEM-CELLS

KW - CROSS-TALK

KW - REPAIR

KW - REGENERATION

KW - EXPRESSION

KW - PATHWAY

KW - PROLIFERATION

U2 - 10.1152/ajplung.00400.2018

DO - 10.1152/ajplung.00400.2018

M3 - Article

VL - 317

SP - L14-L28

JO - American Journal of Physiology - Lung Cellular and Molecular Physiology

JF - American Journal of Physiology - Lung Cellular and Molecular Physiology

SN - 1040-0605

IS - 1

ER -

ID: 79560950