Early lineage specification defines alveolar epithelial ontogeny in the murine lung.

Proc Natl Acad Sci U S A 2019 Feb 19. Epub 2019 Feb 19.

Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104;

During the stepwise specification and differentiation of tissue-specific multipotent progenitors, lineage-specific transcriptional networks are activated or repressed to orchestrate cell specification. The gas-exchange niche in the lung contains two major epithelial cell types, alveolar type 1 (AT1) and AT2 cells, and the timing of lineage specification of these cells is critical for the correct formation of this niche and postnatal survival. Integrating cell-specific lineage tracing studies, spatially specific mRNA transcript and protein expression, and single-cell RNA-sequencing analysis, we demonstrate that specification of alveolar epithelial cell fate begins concomitantly with the proximal-distal specification of epithelial progenitors and branching morphogenesis earlier than previously appreciated. By using a newly developed dual-lineage tracing system, we show that bipotent alveolar cells that give rise to AT1 and AT2 cells are a minor contributor to the alveolar epithelial population. Furthermore, single-cell assessment of the transcriptome identifies specified AT1 and AT2 progenitors rather than bipotent cells during sacculation. These data reveal a paradigm of organ formation whereby lineage specification occurs during the nascent stages of development coincident with broad tissue-patterning processes, including axial patterning of the endoderm and branching morphogenesis.

Download full-text PDF

Source
http://www.pnas.org/lookup/doi/10.1073/pnas.1813952116
Publisher Site
http://dx.doi.org/10.1073/pnas.1813952116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410851PMC
February 2019
24 Reads
9.809 Impact Factor

Publication Analysis

Top Keywords

alveolar epithelial
12
at1 at2
12
lineage specification
12
epithelial cell
8
branching morphogenesis
8
at2 cells
8
specification
7
cells
5
epithelial
5
alveolar
5
progenitors branching
4
epithelial progenitors
4
concomitantly proximal-distal
4
proximal-distal specification
4
specification epithelial
4
appreciated newly
4
dual-lineage tracing
4
tracing system
4
system bipotent
4
developed dual-lineage
4

References

(Supplied by CrossRef)

Similar Publications