| Autor: |
Frank, David B., Penkala, Ian J., Zepp, Jarod A., Sivakumar, Aravind, Linares-Saldana, Ricardo, Zacharias, William J., Stolz, Katharine G., Pankin, Josh, MinQi Lu, Qiaohong Wang, Babu, Apoorva, Li Li, Su Zhou, Morley, Michael P., Jain, Rajan, Morrisey, Edward E. |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/5/2019, Vol. 116 Issue 10, p4362-4371, 10p |
| Abstrakt: |
During the stepwise specification and differentiation of tissuespecific 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 duallineage 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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