Study Describes Genetic Mechanisms Behind Embryonic Lung Cells

In a recent study, researchers described genetic underpinnings of primordial lung progenitors, the embryonic cells that lead to the development of all the cells of the respiratory system lining, which develops after birth, which may have long-term implications for the treatment of diseases affecting the respiratory system, including chronic obstructive pulmonary disease (COPD), alpha-1 antitrypsin deficiency, and cystic fibrosis.

The study was conducted by the Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center, where the researchers used a genetically modified experimental model in order to isolate these early cells and decode their signals.

“Multipotent Nkx2-1-positive lung epithelial primordial progenitors of the foregut endoderm are thought to be the developmental precursors to all adult lung epithelial lineages. However, little is known about the global transcriptomic programs or gene networks that regulate these gateway progenitors in vivo,” the authors explained. “Here we use bulk RNA-sequencing to describe the unique genetic program of in vivo murine lung primordial progenitors and computationally identify signaling pathways, such as Wnt and Tgf-β superfamily pathways, that are involved in their cell-fate determination from pre-specified embryonic foregut.”

Using computational methods, the researchers defined how similar the engineered lung cells in their model were to the in vivo progenitors.

"Our findings define in great detail a rare, transient cell, namely the primordial lung progenitor. The knowledge generated from this study will be of great value in the derivation of human primordial lung progenitors in culture, since the equivalent stage in human lung development is not accessible," author Laertis Ikonomou, PhD, assistant professor of molecular and translational medicine at Boston University School of Medicine, said in a statement.

The researchers suggested that this methodology can be applicable to the creation of tissue progenitors of all germ layers, possibly used for the future development of cell replacement therapies for respiratory diseases.

Additionally, Ikonomou suggested that these findings could lead to more protocols for transplantable lung epithelial cells for drug development and treating diseases, including COPD and cystic fibrosis.

Reference

Ikonomou L, Herriges M, Lewandowski S, et al. The in vivo genetic program of murine primordial lung epithelial progenitors [published online January 31, 2020]. Nature Communications. https://doi.org/10.1038/s41467-020-14348-3.