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Maturation Status of Rat Lung Epithelial Cells in Interspecies Chimeras Generated by Blastocyst Complementation
Yamato Murata1, Shunsuke Yuri1,2, Masahito Ikawa3
1Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.
Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|August 21, 2025
Summary
This study used blastocyst complementation (BC) to generate rat lung epithelial cells in mouse chimeras. While the mouse environment partially promoted lung cell maturation, further mechanisms are needed for full respiratory function.
Area of Science:
- Developmental Biology
- Regenerative Medicine
- Interspecies Chimeras
Background:
- Previous tetraploid complementation produced immature rat lung epithelium in chimeras.
- Fibroblast growth factor receptor 2 (Fgfr2b) plays a role in lung development.
Purpose of the Study:
- To investigate rat lung epithelial cell maturation in interspecies chimeras generated via blastocyst complementation (BC) using Fgfr2b-knockout (KO) mouse embryos.
- To assess the potential of the mouse host environment to support lung development.
Main Methods:
- Generation of Fgfr2b-KO mouse lines using CRISPR/Cas9.
- Injection of GFP-labeled rat embryonic stem (ES) cells into mouse blastocysts.
- Histological analysis and quantitative PCR of lung tissues from chimeras and wild-type rats.
Main Results:
- Blastocyst complementation lungs reached a maturation stage comparable to late-gestation wild-type rat lungs (E20.5-E21.5).
- Expression of key epithelial maturation markers showed inter-individual variability, corresponding to rat lung development stages E19.5-E21.5.
- Rat lung epithelial cells in chimeras exhibited partial maturation, but did not achieve full functional capacity.
Conclusions:
- The mouse host environment partially promotes the maturation of rat-derived lung epithelial cells generated via BC.
- Additional factors or mechanisms are necessary to achieve fully functional respiratory capacity in these interspecies chimeras.
