Characterization of distal airway stem-like cells expressing N-terminally truncated p63 and thyroid transcription factor-1 in the human lung

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Distal airway stem cells (DASCs) in the mouse lung can differentiate into bronchioles and alveoli. However, it remains unclear whether the same stem cells exist in the human lung. Here, we found that human lung epithelial (HuL) cells, derived from normal, peripheral lung tissue, in monolayer, mostly express both the N-terminally truncated isoform of p63 (ΔNp63), a marker for airway basal cells, and thyroid transcription factor-1 (TTF-1), a marker for alveolar epithelial cells, even though these two molecules are usually expressed in a mutually exclusive way. Three-dimensionally cultured HuL cells differentiated to form bronchiole-like and alveolus-like organoids. We also uncovered a few bronchiolar epithelial cells expressing both ΔNp63 and TTF-1 in the human lung, suggesting that these cells are the cells of origin for HuL cells. Taken together, ΔNp63+ TTF-1+ peripheral airway epithelial cells are possibly the human counterpart of mouse DASCs and may offer potential for future regenerative medicine.Graphical abstractHighlightsSome bronchiolar epithelial basal cells express both ΔNp63 and TTF-1 in the lung.These specific cells can form bronchiole-like or alveolus-like organoids.The dual-positive cells can survive and differentiate in the mouse lung.They are a distinct type of peripheral lung epithelial stem cell in the human lung.

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