A Cell-by-Cell Portrait of How Newborns Begin Breathing Air

Published January 2019 | Nature Communications 

The transition from fetal to postnatal life is a sudden storm of complex physiologic and biochemical processes. A rapid series of structural, biochemical, and functional changes help newborns transition from the fluid-filled womb to the gas-filled outside world. Multiple cell types, from the conducting airways to peripheral saccules and alveoli, are involved.

Now a team of Cincinnati Children’s experts led by first author Minzhe Guo and co-corresponding authors Jeffrey Whitsett, MD, and Yan Xu, PhD, has mapped out the changes occurring during this critical stage of life at the most granular level to date. The team used single cell drop-seq and time course RNA sequencing to analyze whole lung tissue from newborn mice. They identified the diversity of pulmonary cells and many associated cellular processes activated at birth, including cell-specific gene signatures, dynamic RNA expression patterns and signaling pathways.

“Among the signaling pathways induced at birth, we demonstrated activation of unfolded protein response (UPR) genes in alveolar epithelial cells, which was accompanied by increased expression of TFs regulating surfactant protein and lipid biosynthesis,” the co-authors state.

Accumulation of misfolded proteins may make the newborn vulnerable to additional environmental challenges, which may contribute to RDS and BPD in preterm infants.

The team identified six distinct epithelial subpopulations, two distinct endothelial cell populations, seven mesenchymal cell subtypes, and five sub-populations of immune cells. All of this data can be used by scientists at Cincinnati Children’s and any other medical center to gain deeper understanding of lung disorders and potentially develop improved therapies.

To help scientists use this valuable data resource, the team developed a web application named “single cells of Lung At Birth” (scLAB).

A photo of Yan Xu, PhD.

Yan Xu, PhD


Guo M, Du Y, Gokey JJ, Ray S, Bell SM, Adam M, Sudha P, Perl AK, Deshmukh H, Potter SS, Whitsett JA, Xu Y. Single cell RNA analysis identifies cellular heterogeneity and adaptive responses of the lung at birth. Nat Commun. Jan 3 2019;10(1):37.