Aquaporin-3 expression in human fetal airway epithelial progenitor cells
Aquaporin-3 expression in human fetal airway epithelial progenitor cells
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DOI：
10.1634/stemcells.2004-0197
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发表时间：
2005-08-01
期刊：
影响因子：
5.2
通讯作者：
Péault, B
中科院分区：
文献类型：
--
作者：
Avril-Delplanque, A;Casal, I;Péault, B
气道上皮干细胞尚未被前瞻性地鉴定，但一般认为分泌细胞和基底细胞都具有分裂和分化的能力。此前，我们开发了一种检测人类气道上皮祖细胞的方法，依赖于将胎儿呼吸组织移植到免疫缺陷小鼠体内。在本研究中，我们假设气道再生上皮祖细胞可以用表面抗原进行标记，并筛选了一系列这样的候选标记，包括凝集素配体、CD44和CD166粘附分子以及水通道蛋白-3 （AQP3）水通道。我们观察到AQP3在基底细胞表面选择性表达，通过流式细胞术可以分离AQP3（+）基底细胞和AQP3（-）纤毛细胞和分泌细胞。体内分选细胞的功能评价表明，AQP3（+）细胞可以恢复正常的假层状粘膜纤毛上皮和粘膜下腺体。AQP3（-）细胞也被赋予类似的潜能，尽管更快的植入表明它们包含了更多承诺的祖细胞。这些结果表明，人类气管-支气管粘膜中的候选干细胞可以通过一种新的标记物积极选择，而且，这也是第一次，上皮祖细胞存在于人类气道内的基底细胞和超基底细胞亚群中。
Airway epithelium stem cells have not yet been prospectively identified, but it is generally assumed that both secretory and basal cells have the capacity to divide and differentiate. Previously, we developed a test for progenitor cells of the human airway epithelium, relying on the transplantation of fetal respiratory tissues into immunodeficient mice. In this study, we hypothesized that airway-repopulating epithelial progenitors can be marked with surface antigens, and we screened an array of such candidate markers, including lectin ligands, the CD44 and CD166 adhesion molecules, and the aquaporin-3 (AQP3) water channel. We observed that AQP3 is selectively expressed on the surface of basal cells, allowing the separation by flow cytometry of AQP3(+) basal cells and AQP3(-) ciliated and secretory cells. Functional evaluation of sorted cells in vivo showed that AQP3(+) cells can restore a normal pseudostratified, mucociliary epithelium as well as submucosal glands. AQP3(-)cells are also endowed with a similar potential, although faster engraftment suggests their inclusion of more committed progenitors. These results show that stem cell candidates in the human tracheo-bronchial mucosa can be positively selected with a novel marker but also, for the first time, that epithelial progenitors exist among both basal and supra-basal cell subsets within the human airway.