Endogenous Fibroblastic Progenitor Cells in the Adult Mouse Lung Are Highly Enriched in the Sca-1 Positive Cell Fraction
Endogenous Fibroblastic Progenitor Cells in the Adult Mouse Lung Are Highly Enriched in the Sca-1 Positive Cell Fraction
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DOI：
10.1634/stemcells.2008-0866
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发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Bertoncello, Ivan
中科院分区：
文献类型：
--
作者：
McQualter, Jonathan L.;Brouard, Nathalie;Bertoncello, Ivan
Sca-1 抗原最初被确定为小鼠造血干细胞的特异性标记物，后来发现，候选干细胞在成年小鼠的血管内皮、骨骼肌、乳腺和前列腺等组织中差异表达。在成年小鼠肺中，Sca-1 先前已被鉴定为分离候选非造血 (CD45(-))、非内皮 (CD31(-)) 支气管肺泡干细胞 (BASC) 的选择性标记，这些细胞位于支气管肺泡管连接处，共表达表面活性剂蛋白 C 和 Clara 细胞特异性蛋白。我们对胎儿、新生儿和成人肺中 CD45(-)CD31(-)Sca-1(+) 细胞的系统分析表明，这些细胞在出生前很少能被检测到，但在出生后呈指数增长，与肺发育从囊泡阶段到肺泡阶段的转变相一致。与候选 BASC 不同，我们描述的 CD45(-)CD31(-)Sca-1(+) CD34(+) 细胞部分共表达免疫表型标记 Thy-1 和血小板衍生生长因子受体 α)。内肺。纤维母细胞而不是上皮细胞。 CD45(-)CD31(-)Sca-1(+)CD34(+)细胞部分的间充质“特征”通过转录谱、证明克隆性脂肪、成纤维细胞和非脂肪成纤维细胞祖细胞富集的细胞培养研究以及肺实质血管周围细胞中Sca-1的免疫组织化学定位进一步证实。 CD45(-)CD31(-)Sca-1(+)CD34(+)细胞表型确实如此。对于成年小鼠肺中的内源性克隆祖细胞，我们的数据表明这些祖细胞主要代表间充质细胞谱系，并强调迫切需要鉴定替代标记和稳健的功能测定。阳离子和表征 上皮和.成人肺中的成纤维细胞干细胞和祖细胞群。干细胞2009； 27：623 - 633
Originally identified as a marker specifying murine hematopoietic stem cells, the Sca-1 antigen has since been shown to be differentially expressed by candidate stem cells in tissues including vascular endothelium, skeletal muscle, mammary gland, and prostate of adult mice. In the adult murine lung, Sca-1 has previously been identified as a selectable marker for the isolation of candidate nonhematopoietic (CD45(-)), nonendothelial (CD31(-)) bronchioalveolar stem cells (BASC) located at the bronchioalveolar duct junction that coexpress surfactant protein C and the Clara cell specific protein. Our systematic analysis of CD45(-)CD31(-)Sca-1(+) cells in fetal, neonatal, and adult lung shows that very few of these cells are detectable prior to birth but expand exponentially postnatally coinciding with the transition from the saccular to the alveolar stage of lung development. Unlike candidate BASCs, the CD45(-)CD31(-)Sca-1(+) CD34(+) cell fraction we describe coexpresses immunophenotypic markers Thy-1 and platelet-derived growth factor receptor alpha) that de. ne lung. broblastic rather than epithelial cells. The mesenchymal "signature'' of the CD45(-)CD31(-)Sca-1(+)CD34(+) cell fraction is further confirmed by transcriptional pro. ling, by cell culture studies demonstrating enrichment for clonogenic lipo. broblastic and nonlipofibroblastic progenitors, and by immunohistochemical localization of Sca-1 in perivascular cells of the lung parenchyma. Although the CD45(-)CD31(-)Sca-1(+)CD34(+) cell phenotype does de. ne endogenous clonogenic progenitor cells in the adult murine lung, our data indicate that these progenitors are predominantly representative of mesenchymal cell lineages, and highlights the pressing need for the identification of alternative markers and robust functional assays for the identi. cation and characterization of epithelial and. broblastic stem and progenitor cell populations in the adult lung. STEM CELLS 2009; 27: 623 - 633