Pluto Bioinformatics

GSE108975: Von Hippel-Lindau protein is required for optimal alveolar macrophage terminal differentiation, self-renewal and function.

Bulk RNA sequencing

The rapid transit from hypoxia to normoxia in the lung that follows the first breath in newborn mice coincides with alveolar macrophage (AM) differentiation. However, whether sensing of oxygen fluctuation contributes to AM maturation and function has not been previously explored. We have generated mice whose AMs show a deficient ability to sense oxygen after birth by deleting VHL, the master negative regulator of HIF transcription factors, in the CD11c compartment (CD11cVhl mice). VHL-deficient AMs show an immature-like phenotype and an impaired self-renewal capacity in vivo that persists upon culture ex vivo. Unlike AMs transplanted from control Vhlfl/fl mice, AMs from CD11cVhl mice do not reverse pulmonary alveolar proteinosis when transplanted into Csf2rb-/- mice, demonstrating that VHL contributes to AM-mediated surfactant clearance. Thus, our results suggest that optimal AM terminal differentiation, self-renewal, and homeostatic function may be influenced by their oxygen sensing capacity after birth. SOURCE: Manuel,J,Gomez (mjgomezr@cnic.es) - Bioinformatics Unit CNIC