/ Poster Discussion Session D28 MAKING REPARATIONS: MESENCHYMAL STEM CELLS AND FIBROCYTES IN LUNG DISEASE / Wednesday, May 22/8:15 AM-10:45 AM / Room 108 A-B (100 Level) Pennsylvania Convention Center Yy1 Participates In The Differentiation Of Bone Marrow-Derived Cells To Fibroblasts And Fibrocytes , P. J. Sime , J. Guo 1 1 University of Rochester, Rochester, NY 1 Corresponding author's email: [email protected] Rationale: Fibrocytes are bone marrow-derived mesenchymal cell precursors, defined primarily by their ability to co-express markers of both hematopoietic (e.g. CD45 or CXCR4) and stromal (e.g. collagen) lineages. The varied levels of fibrocytes in blood have raised considerable interest in their use as a biomarker of pulmonary fibrosis. It has been reported that the transcription factor Yin Yang 1 (YY1) plays an important role in cell differentiation. It directly regulates alpha smooth muscle actin (alpha-SMA) and collagen expression in lung fibroblasts. However, the role of YY1 in promoting bone marrow cell differentiation to fibrocytes or myofibroblast-like cells, and its role in tissue injury/repair remain poorly defined. We hypothesize that YY1 promotes differentiation of bone marrow cells to fibrocytes/fibroblast-like cells. Method: Bleomycin was administrated to wild type C57BL6 and YY1 deficient mice by oropharyngeal aspiration. Primary bone marrow cells and PBMCs were isolated from control mice or mice treated with bleomycin. YY1, alpha-SMA and collagen expression were determined by western blot, immunofluorescent staining and quantitative PCR to analyze both gene and protein expression and to determine bone marrow cell differentiation. CD45, CXCR4 and collagen were determined by flow cytometry to examine their regulation following bleomycin-induced lung injury. Results: YY1, CD45, CXCR4 and collagen positive cells were all increased in bone marrow cells and PBMCs of mice treated by bleomycin compared to saline treated mice. Interestingly, alpha-SMA was also increased in the bone marrow cells of bleomycin-treated mice. Knockout of YY1 decreased bone marrow cell differentiation of fibroblast-like cells with reduction in alpha-SMA and collagen expression. Conclusion: Following bleomycin-induced lung injury bone marrow cells differentiate to fibrocytes or fibroblast-like cells during repair. This differentiation is regulated, at least in part, by YY1 expression. This abstract is funded by: ATS 214017, AHA 11SDG560007, NIH HL75432, Connor fund Am J Respir Crit Care Med 187;2013:A5415 Internet address: www.atsjournals.org Online Abstracts Issue

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/ Poster Discussion SessionD28 MAKING REPARATIONS: MESENCHYMAL STEM CELLS AND FIBROCYTES IN LUNG DISEASE/ Wednesday, May 22/8:15 AM-10:45 AM / Room 108 A-B (100 Level) Pennsylvania Convention Center

Yy1 Participates In The Differentiation Of Bone Marrow-Derived Cells To Fibroblasts And Fibrocytes

, P. J. Sime ,J. Guo1 1

University of Rochester, Rochester, NY1

Corresponding author's email: [email protected]

Rationale: Fibrocytes are bone marrow-derived mesenchymal cell precursors, defined primarily by their ability to co-express markers ofboth hematopoietic (e.g. CD45 or CXCR4) and stromal (e.g. collagen) lineages. The varied levels of fibrocytes in blood have raisedconsiderable interest in their use as a biomarker of pulmonary fibrosis. It has been reported that the transcription factor Yin Yang 1 (YY1)plays an important role in cell differentiation. It directly regulates alpha smooth muscle actin (alpha-SMA) and collagen expression in lungfibroblasts. However, the role of YY1 in promoting bone marrow cell differentiation to fibrocytes or myofibroblast-like cells, and its role intissue injury/repair remain poorly defined. We hypothesize that YY1 promotes differentiation of bone marrow cells tofibrocytes/fibroblast-like cells. Method: Bleomycin was administrated to wild type C57BL6 and YY1 deficient mice by oropharyngealaspiration. Primary bone marrow cells and PBMCs were isolated from control mice or mice treated with bleomycin. YY1, alpha-SMA andcollagen expression were determined by western blot, immunofluorescent staining and quantitative PCR to analyze both gene andprotein expression and to determine bone marrow cell differentiation. CD45, CXCR4 and collagen were determined by flow cytometry toexamine their regulation following bleomycin-induced lung injury. Results: YY1, CD45, CXCR4 and collagen positive cells were allincreased in bone marrow cells and PBMCs of mice treated by bleomycin compared to saline treated mice. Interestingly, alpha-SMA wasalso increased in the bone marrow cells of bleomycin-treated mice. Knockout of YY1 decreased bone marrow cell differentiation offibroblast-like cells with reduction in alpha-SMA and collagen expression. Conclusion: Following bleomycin-induced lung injury bonemarrow cells differentiate to fibrocytes or fibroblast-like cells during repair. This differentiation is regulated, at least in part, by YY1expression.

This abstract is funded by: ATS 214017, AHA 11SDG560007, NIH HL75432, Connor fundAm J Respir Crit Care Med 187;2013:A5415

Internet address: www.atsjournals.org Online Abstracts Issue