Identification of a novel multipotent cell lineage in the lung

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	DEV-6

* FARE Award Winner

Authors

• Y Li
• I Linnoila

Abstract

Multiple cell phenotypes contribute to the structure and function of the lung. They include alveolar type I, type II, Clara and ciliated cells. Pulmonary neuroendocrine cells (PNEC) represent a small but important cell population in the airways. PNECs regulate breathing and may contribute to carcinogenesis, but their histogenesis has remained elusive. Ascl1, a neural transcription factor critical for PNEC development, regulates stem cell markers in the lung. To understand whether Ascl1-defined cells (ADCs) function as progenitors, we used in vivo lineage tracing approach to follow ADC fate during lung development. Rosa reporter mice were crossed with Ascl1-CreERTM (AC) mice, in which Ascl1 promoter drives the expression of inducible Cre recombinase. ADCs and their descendants are permanently labeled after tamoxifen administration to Rosa dams. The identities of labeled cells were characterized by immunohistochemistry. Interestingly, ADCs labeled at embryonic day E9.5 gave rise to both airway cells (PNECs, Clara, and ciliated cells) and alveolar cells (type II cells). However, ADCs labeled at E11.5 gave rise to airway cells only. We conclude that neuroendocrine (NE) cell lineage in the developing lungs is not limited to mature PNECs, but also includes progenitors for non-NE cells, e.g. Clara, ciliated, and alveolar type II cells.

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