title: Myeloid-specific expression of Stat3C results in conversion of bone marrow mesenchymal stem cells into alveolar type II epithelial cells in the lung.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-5188, USA. coyan@iupui.edu
authors.forename: Cong
authors.initials: C
authors.lastname: Yan
authors.forename: Peng
authors.initials: P
authors.lastname: Qu
authors.forename: Hong
authors.initials: H
authors.lastname: Du
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse