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Interleukin‐6 induces the lineage commitment of bone marrow‐derived mesenchymal multipotent cells through down‐regulation of Sox2 by osteogenic transcription factors
Author(s) -
Yoon Dong Suk,
Kim Yun Hee,
Lee Seulgi,
Lee KyoungMi,
Park Kwang Hwan,
Jang Yeonsue,
Lee Jin Woo
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-248567
Subject(s) - multipotent stem cell , microbiology and biotechnology , sox2 , mesenchymal stem cell , stromal cell , bone marrow , biology , runx2 , population , stem cell , immunology , progenitor cell , transcription factor , cancer research , medicine , genetics , gene , environmental health
Bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) are a heterogeneous population of cells that differ in size and morphology. BM‐MSCs become committed to the osteogenic lineage as senescence approaches and lose multipotency. Nevertheless, little is known about the effects of cell‐cell interaction between different populations on stemness loss and lineage commitment. The current study aimed to identify mechanisms by which cell‐cell interactions between heterogeneous BM‐MSCs affect stemness and lineage commitment of multipotent subpopulation. The lineage commitment of primitive multipotent cells was strongly induced in the presence of cytokines secreted by senescent‐like cells in a cell culture insert system. Senescent‐like cells secreted higher levels of interleukin‐6 (IL‐6) than primitive multipotent cells in a human cytokine array. IL‐6 induced the lineage commitment and stemness loss in multipotent cells by decreasing Sox2 expression. Furthermore, we confirmed that IL‐6 decreased the transcriptional activity of Sox2 through up‐regulation of Runx2 and Dlx5. We suggest a mechanism by which IL‐6 modulates the expression of Sox2, resulting in decreased multipotency and causing primitive multipotent cells to undergo osteogenic lineage commitment. This is the first study to identify mechanisms in which the cell‐cell interactions between the different populations play important roles in the stemness loss and lineage commitment of multipotent populations.—Yoon, D. S., Kim, Y. H., Lee, S., Lee, K.‐M., Park, K. H., Jang, Y., Lee, J. W. Interleukin‐6 induces the lineage commitment of bone marrow‐derived mesenchymal multipotent cells through down‐regulation of Sox2 by osteogenic transcription factors. FASEB J . 28, 3273–3286 (2014). www.fasebj.org