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Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs
Authors: H. Lee, Michelle
Goralczyk, Anna G.
Kriszt, Rókus
Ang, Xiu Min
Badowski, Cedric
Li, Ying
Summers, Scott A.
Toh, Sue-Anne
Yassin, M. Shabeer
Shabbir, Asim
Sheppard, Allan
Raghunath, Michael
DOI: 10.21256/zhaw-4752
Published in: Scientific Reports
Volume(Issue): 6
Issue: 21173
Issue Date: 2016
Publisher / Ed. Institution: Nature Publishing Group
ISSN: 2045-2322
Language: English
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.
Fulltext version: Published version
License (according to publishing contract): CC BY 4.0: Attribution 4.0 International
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:Publikationen Life Sciences und Facility Management

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