Open AccessLow oxygen tension enhances the generation of lung progenitor cells from mouse embryonic and induced pluripotent stem cells
Author(s) -
Garreta Elena,
Melo Esther,
Navajas Daniel,
Farré Ramon
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12075
Subject(s) - induced pluripotent stem cell , oxygen tension , embryonic stem cell , progenitor cell , microbiology and biotechnology , lung , stem cell , biology , oxygen , chemistry , medicine , biochemistry , gene , organic chemistry
Whole‐organ decellularization technology has emerged as a new alternative for the fabrication of bioartificial lungs. Embryonic stem cells ( ESC ) and induced pluripotent stem cells (iPSC) are potentially useful for recellularization since they can be directed to express phenotypic marker genes of lung epithelial cells. Normal pulmonary development takes place in a low oxygen environment ranging from 1 to 5%. By contrast, in vitro ESC and i PSC differentiation protocols are usually carried out at room‐air oxygen tension. Here, we sought to determine the role played by oxygen tension on the derivation of Nkx2.1+ lung/thyroid progenitor cells from mouse ESC and i PSC . A step‐wise differentiation protocol was used to generate Nkx2.1+ lung/thyroid progenitors under 20% and 5% oxygen tension. On day 12, gene expression analysis revealed that Nkx2.1 and Foxa2 (endodermal and early lung epithelial cell marker) were significantly upregulated at 5% oxygen tension in ESC and i PSC differentiated cultures compared to 20% oxygen conditions. In addition, quantification of Foxa2+Nkx2.1+Pax8‐ cells corresponding to the lung field, with exclusion of the potential thyroid fate identified by Pax8 expression, confirmed that the low physiologic oxygen tension exerted a significant positive effect on early pulmonary differentiation of ESC and i PSC . In conclusion, we found that 5% oxygen tension enhanced the derivation of lung progenitors from mouse ESC and i PSC compared to 20% room‐air oxygen tension.