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|Title:||ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs|
|Authors :||H. Lee, Michelle|
Goralczyk, Anna G.
Ang, Xiu Min
Summers, Scott A.
Yassin, M. Shabeer
|Published in :||Scientific Reports|
|Publisher / Ed. Institution :||Nature Publishing Group|
|License (according to publishing contract) :||CC BY 4.0: Attribution 4.0 International|
|Type of review:||Peer review (publication)|
|Subject (DDC) :||571: Physiology and related subjects |
610: Medicine and health
|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.|
|Departement:||Life Sciences and Facility Management|
|Organisational Unit:||Institute of Chemistry and Biotechnology (ICBT)|
|Publication type:||Article in scientific journal|
|Appears in Collections:||Publikationen Life Sciences und Facility Management|
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|2016_Lee_et_al_ECM_microenvironment_unlocks_brown_adipogenic_potential.pdf||3.71 MB||Adobe PDF|
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