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.
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Biographical Sketch Dr. Yan Cong graduated from Wuhan University in 1982 with a BS degree of virology. He is a class I member of the CUSBEA (China-United States Biochemistry Examination and Application) Program in 1982, and received his Ph.D. degree of biochemistry from the City University of New York in 1987. He was trained as a post-doctor by Dr. Igor Tamm (National Academy Member of Science, USA) from 1987 to 1990 at The Rockefeller University in New York. He is currently a Professor at the Department of Pathology and Laboratory Medicine, a Member of the Center for Immunobiology, a Member of Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA.
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Yan, C., Qu, P. & Du, H. Myeloid-specific expression of Stat3C results in conversion of bone marrow mesenchymal stem cells into alveolar type II epithelial cells in the lung. Sci. China Life Sci. 55, 576–590 (2012). https://doi.org/10.1007/s11427-012-4339-2
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DOI: https://doi.org/10.1007/s11427-012-4339-2