Dataset Information

The potential of brown adipogenesis and browning in porcine bone marrow-derived mesenchymal stem cells1.

ABSTRACT: Brown adipocyte lineage commitment and differentiation are under complex regulation. Brown adipocytes are derived from mesenchymal stem cells (MSC). Whether porcine bone marrow-derived MSC (BM-MSC) possess the potential to differentiate into brown adipocytes remains unclear. In the current study, we evaluated the ability of porcine BM-MSC to differentiate into brown adipocytes and browning of differentiated adipocytes. We found that similar to rodent models, bone morphogenetic protein 7 (BMP7) was able to trigger the commitment of BM-MSC to the brown adipocyte lineage by elevating expression of marker genes, nrf-1, tfam, zic1, and pgc-1? (P < 0.05). The expression of brown adipocyte-specific genes, prdm16, dio2, and cidea, was significantly induced (P < 0.05) in BMP7-treated porcine BM-MSC after hormonal induction of adipogenesis. The UCP2 and UCP3 protein levels in BMP7-treated porcine BM-MSC were higher than the control group after hormonal induction of adipogenesis, accompanied by increased mitochondrial DNA copy number and mitochondria-specific gene expression (P < 0.05). Furthermore, acute norepinephrine stimulation potentiated brown adipocyte-specific mRNA expression (P < 0.05) in differentiated adipocytes. Similarly, UCP2 and UCP3 protein levels were increased in differentiated adipocytes upon acute norepinephrine stimulation. In addition, mitochondrial DNA copy number and mitochondria-specific gene expression were also significantly increased (P < 0.05) in differentiated adipocytes after acute norepinephrine exposure. Taken together, these results demonstrate for the first time that porcine BM-MSC are able to commit to the brown adipocyte lineage and differentiate into brown adipocytes. Differentiated adipocytes derived from porcine BM-MSC have the developmental potential to transdifferentiate into brown-like adipocytes upon norepinephrine stimulation.

SUBMITTER: Chen YC

PROVIDER: S-EPMC6127779 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The potential of brown adipogenesis and browning in porcine bone marrow-derived mesenchymal stem cells1.

Chen Ying-Chu YC Yu Yu-Hsiang YH

Journal of animal science 20180901 9

Brown adipocyte lineage commitment and differentiation are under complex regulation. Brown adipocytes are derived from mesenchymal stem cells (MSC). Whether porcine bone marrow-derived MSC (BM-MSC) possess the potential to differentiate into brown adipocytes remains unclear. In the current study, we evaluated the ability of porcine BM-MSC to differentiate into brown adipocytes and browning of differentiated adipocytes. We found that similar to rodent models, bone morphogenetic protein 7 (BMP7) w ...[more]

PMID: 29878130

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Project description:UnlabelledMesenchymal stem cells (MSCs) can differentiate into multiple lineages through guidance from the biophysical and biochemical properties of the extracellular matrix. In this work we conduct a combinatorial study of matrix properties that influence adipogenesis and neurogenesis including: adhesion proteins, stiffness, and cell geometry, for mesenchymal stem cells derived from adipose tissue (AT-MSCs) and bone marrow (BM-MSCs). We uncover distinct differences in integrin expression, the magnitude of traction stress, and lineage specification to adipocytes and neuron-like cells between cell sources. In the absence of media supplements, adipogenesis in AT-MSCs is not significantly influenced by matrix properties, while the converse is true in BM-MSCs. Both cell types show changes in the expression of neurogenesis markers as matrix cues are varied. When cultured on laminin conjugated microislands of the same adhesive area, BM-MSCs display elevated adipogenesis markers, while AT-MSCs display elevated neurogenesis markers; integrin analysis suggests neurogenesis in AT-MSCs is guided by adhesion through integrin αvβ3. Overall, the properties of the extracellular matrix guides MSC adhesion and lineage specification to different degrees and outcomes, in spite of their similarities in general characteristics. This work will help guide the selection of MSCs and matrix components for applications where high fidelity of differentiation outcome is desired.Statement of significanceMesenchymal stem cells (MSCs) are an attractive cell type for stem cell therapies; however, in order for these cells to be useful in medicine, we need to understand how they respond to the physical and chemical environments of tissue. Here, we explore how two promising sources of MSCs-those derived from bone marrow and from adipose tissue-respond to the compliance and composition of tissue using model extracellular matrices. Our results demonstrate a source-specific propensity to undergo adipogenesis and neurogenesis, and uncover a role for adhesion, and the degree of traction force exerted on the substrate in guiding these lineage outcomes.

Project description:The microenvironment plays a vital role in both the maintenance of stem cells in their undifferentiated state (niche) and their differentiation after homing into new locations outside this niche. Contrary to conventional in-vitro culture practices, the in-vivo stem cell microenvironment is physiologically crowded. We demonstrate here that re-introducing macromolecular crowding (MMC) at biologically relevant fractional volume occupancy during chemically induced adipogenesis substantially enhances the adipogenic differentiation response of human bone marrow-derived mesenchymal stem cells (MSCs). Both early and late adipogenic markers were significantly up-regulated and cells accumulated 25-40% more lipid content under MMC relative to standard induction cocktails. MMC significantly enhanced deposition of extracellular matrix (ECM), notably collagen IV and perlecan, a heparan sulfate proteoglycan. As a novel observation, MMC also increased the presence of matrix metalloproteinase -2 in the deposited ECM, which was concomitant with geometrical ECM remodeling typical of adipogenesis. This suggested a microenvironment that was richer in both matrix components and associated ligands and was conducive to adipocyte maturation. This assumption was confirmed by seeding undifferentiated MSCs on decellularized ECM deposited by adipogenically differentiated MSCs, Adipo-ECM. On Adipo-ECM generated under crowding, MSCs differentiated much faster under a classical differentiation protocol. This was evidenced throughout the induction time course, by a significant up-regulation of both early and late adipogenic markers and a 60% higher lipid content on MMC-generated Adipo-ECM in comparison to standard induction on tissue culture plastic. This suggests that MMC helps build and endow the nascent microenvironment with adipogenic cues. Therefore, MMC initiates a positive feedback loop between cells and their microenvironment as soon as progenitor cells are empowered to build and shape it, and, in turn, are informed by it to respond by attaining a stable differentiated phenotype if so induced. This work sheds new light on the utility of MMC to tune the microenvironment to augment the generation of adipose tissue from differentiating human MSCs.

Dataset Information

The potential of brown adipogenesis and browning in porcine bone marrow-derived mesenchymal stem cells1.

Publications

The potential of brown adipogenesis and browning in porcine bone marrow-derived mesenchymal stem cells1.

Similar Datasets

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