TY  - JOUR
A1  - Dotterweich, Julia
A1  - Schlegelmilch, Katrin
A1  - Keller, Alexander
A1  - Geyer, Beate
A1  - Schneider, Doris
A1  - Zeck, Sabine
A1  - Tower, Robert J. J.
A1  - Ebert, Regina
A1  - Jakob, Franz
A1  - Schütze, Norbert
T1  - Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells-implications for myeloma bone disease
JF  - Bone
N2  - Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA6 cell attachment. This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage.
KW  - marrow stromal cells
KW  - Endothelial growth-factor
KW  - precedes multiple-myeloma
KW  - monoclonial gammopathy
KW  - in-vitro
KW  - mesenchymal stem-cells
KW  - undetermined significance
KW  - angiogenic cytokines
KW  - peripheral-blood
KW  - gene-expression
KW  - Multiple myeloma
KW  - Bone disease
KW  - Angiopoietin-like 4
KW  - Gene expression profiling
KW  - Mesenchymal stem cells
KW  - Osteogenic precursor cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186688
VL  - 93
ER  - 
TY  - JOUR
A1  - Mayr, Antonia V.
A1  - Keller, Alexander
A1  - Peters, Marcell K.
A1  - Grimmer, Gudrun
A1  - Krischke, Beate
A1  - Geyer, Mareen
A1  - Schmitt, Thomas
A1  - Steffan‐Dewenter, Ingolf
T1  - Cryptic species and hidden ecological interactions of halictine bees along an elevational gradient
JF  - Ecology and Evolution
N2  - Changes of abiotic and biotic conditions along elevational gradients represent serious challenges to organisms which may promote the turnover of species, traits and biotic interaction partners. Here, we used molecular methods to study cuticular hydrocarbon (CHC) profiles, biotic interactions and phylogenetic relationships of halictid bees of the genus Lasioglossum along a 2,900 m elevational gradient at Mt. Kilimanjaro, Tanzania. We detected a strong species turnover of morphologically indistinguishable taxa with phylogenetically clustered cryptic species at high elevations, changes in CHC profiles, pollen resource diversity, and a turnover in the gut and body surface microbiome of bees. At high elevations, increased proportions of saturated compounds in CHC profiles indicate physiological adaptations to prevent desiccation. More specialized diets with higher proportions of low‐quality Asteraceae pollen imply constraints in the availability of food resources. Interactive effects of climatic conditions on gut and surface microbiomes, CHC profiles, and pollen diet suggest complex feedbacks among abiotic conditions, ecological interactions, physiological adaptations, and phylogenetic constraints as drivers of halictid bee communities at Mt. Kilimanjaro.
KW  - COI
KW  - cuticular chemistry
KW  - elevational gradient
KW  - Halictidae
KW  - microbiome metabarcoding
KW  - pollen metabarcoding
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238853
VL  - 11
IS  - 12
SP  - 7700
EP  - 7712
ER  -