Early lineage specification defines alveolar epithelial ontogeny in the murine lung.
Proc Natl Acad Sci U S A
; 116(10): 4362-4371, 2019 03 05.
Article
em En
| MEDLINE
| ID: mdl-30782824
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Alvéolos Pulmonares
/
Linhagem da Célula
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Pulmão
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article