Myeloid-specific expression of Stat3C results in conversion of bone marrow mesenchymal stem cells into alveolar type II epithelial cells in the lung.
Myeloid-specific expression of Stat3C results in conversion of bone marrow mesenchymal stem cells into alveolar type II epithelial cells in the lung.
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DOI：
10.1007/s11427-012-4339-2
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Du H
中科院分区：
文献类型：
--
作者：
Yan C;Qu P;Du H
骨髓间充质干细胞（BMSCs）和髓系细胞均来源于骨髓，在体内相互影响。为了阐明控制这两种细胞类型之间相互关系的机制，在新建立的c-fms-rtTA/（TetO）7-CMV-Stat 3C双转基因小鼠模型中，通过过表达Stat 3C来激活信号转导和转录激活因子3（Stat 3）的信号通路。在该系统中，Stat 3C-Flag融合蛋白在多西环素处理后的髓系细胞中过表达。Stat 3C过表达诱导多个器官中巨噬细胞和中性粒细胞的系统性升高。在肺中，观察到组织肿瘤性肺细胞增殖。将体外培养的hSP-B 1.5kb lacZ BMSCs注射入双转基因小鼠体内，BMSCs可在多个器官中增殖，并在骨髓和脾脏中自我更新，转化为肺泡Ⅱ型上皮细胞。骨髓移植研究表明，髓系细胞和BMSC-AT II细胞转化的增加是由于Stat 3C过表达导致的髓系祖细胞功能障碍。该研究支持了髓样细胞中Stat 3通路的激活在BMSC功能中起重要作用的概念，包括归巢，重新增殖和转化为肺中的住宅AT II上皮细胞。
Bone marrow mesenchymal stem cells (BMSCs) and myeloid lineage cells originate from the bone marrow, and influence each other in vivo. To elucidate the mechanism that controls the interrelationship between these two cell types, the signaling pathway of signal transducer and activator of transcription 3 (Stat3) was activated by overexpressing Stat3C in a newly established c-fms-rtTA/(TetO)7-CMV-Stat3C bitransgenic mouse model. In this system, Stat3C-Flag fusion protein was overexpressed in myeloid lineage cells after doxycycline treatment. Stat3C overexpression induced systematic elevation of macrophages and neutrophils in multiple organs. In the lung, tissue neoplastic pneumocyte proliferation was observed. After in vitro cultured hSP-B 1.5-kb lacZ BMSCs were injected into the bitransgenic mice, BMSCs were able to repopulate in multiple organs, self-renew in the bone marrow and spleen, and convert into alveolar type II epithelial cells. The bone marrow transplantation study indicated that increases of myeloid lineage cells and BMSC-AT II cell conversion were due to malfunction of myeloid progenitor cells as a result of Stat3C overexpression. The study supports the concept that activation of the Stat3 pathway in myeloid cells plays an important role in BMSC function, including homing, repopulating and converting into residential AT II epithelial cells in the lung.
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影响因子：
11.2
作者：
Li, Yuan;Du, Hong;Yan, Cong
通讯作者：
Yan, Cong
影响因子：
4
作者：
Baddoo, M;Hill, K;Phinney, DG
通讯作者：
Phinney, DG
影响因子：
6
作者：
Qu, Peng;Shelley, William C.;Yan, Cong
通讯作者：
Yan, Cong
影响因子：
20.3
作者：
Qu, Peng;Yan, Cong;Du, Hong
通讯作者：
Du, Hong
影响因子：
4.4
作者：
Lian, XM;Qin, YL;Yan, C
通讯作者：
Yan, C