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Title: ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs
Authors: Lee, M.H 
Goralczyk, A.G 
Kriszt, R
Ang, X.M
Badowski, C
Li, Y
Summers, S.A
Toh, S.-A 
Yassin, M.S 
Shabbir, A 
Sheppard, A
Raghunath, M 
Keywords: activating transcription factor 2
uncoupling protein 1
abdominal subcutaneous fat
biological model
brown adipocyte
cell differentiation
extracellular matrix
gene expression
mesenchymal stroma cell
tumor microenvironment
white adipocyte
Activating Transcription Factor 2
Adipocytes, Brown
Adipocytes, White
Cell Differentiation
Cellular Microenvironment
Extracellular Matrix
Gene Expression
Mesenchymal Stromal Cells
Models, Biological
Subcutaneous Fat, Abdominal
Uncoupling Protein 1
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Lee, M.H, Goralczyk, A.G, Kriszt, R, Ang, X.M, Badowski, C, Li, Y, Summers, S.A, Toh, S.-A, Yassin, M.S, Shabbir, A, Sheppard, A, Raghunath, M (2016). ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs. Scientific Reports 6 : 21173. ScholarBank@NUS Repository.
Abstract: Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced 'browning' in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow.
Source Title: Scientific Reports
ISSN: 20452322
DOI: 10.1038/srep21173
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