TY - JOUR A1 - Franke, Katharina A1 - Vilne, Baiba A1 - da Costa, Olivia Prazeres A1 - Rudelius, Martina A1 - Peschel, Christian A1 - Oostendorp, Robert A. J. A1 - Keller, Ulrich T1 - In vivo hematopoietic Myc activation directs a transcriptional signature in endothelial cells within the bone marrow microenvironment JF - Oncotarget N2 - Cancer pathogenesis involves tumor-intrinsic genomic aberrations and tumor-cell extrinsic mechanisms such as failure of immunosurveillance and structural and functional changes in the microenvironment. Using Myc as a model oncogene we established a conditional mouse bone marrow transduction/transplantation model where the conditional activation of the oncoprotein Myc expressed in the hematopoietic system could be assessed for influencing the host microenvironment. Constitutive ectopic expression of Myc resulted in rapid onset of a lethal myeloproliferative disorder with a median survival of 21 days. In contrast, brief 4-day Myc activation by means of the estrogen receptor (ER) agonist tamoxifen did not result in gross changes in the percentage/frequency of hematopoietic lineages or hematopoietic stem/progenitor cell (HSPC) subsets, nor did Myc activation significantly change the composition of the non-hematopoietic microenvironment defined by phenotyping for CD31, ALCAM, and Sca-1 expression. Transcriptome analysis of endothelial CD45-Ter119-cells from tamoxifen-treated MycER bone marrow graft recipients revealed a gene expression signature characterized by specific changes in the Rho subfamily pathway members, in the transcription-translation-machinery and in angiogenesis. In conclusion, intra-hematopoietic Myc activation results in significant transcriptome alterations that can be attributed to oncogene-induced signals from hematopoietic cells towards the microenvironment, e. g. endothelial cells, supporting the idea that even pre-leukemic HSPC highjack components of the niche which then could protect and support the cancer-initiating population. KW - stem-cells KW - mutations KW - C-Myc KW - Rho-GTPases KW - niche KW - leukemia KW - target KW - growth KW - cycle KW - apoptosis, Myc KW - microenvironment KW - endothelial cells Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145844 VL - 6 IS - 26 SP - 21827 EP - 21839 ER - TY - JOUR A1 - Pereira, A. R. A1 - Trivanović, D. A1 - Herrmann, M. T1 - Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro JF - European Cells and Materials N2 - Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications. The present comprehensive review extensively discusses the microenvironmental cues that influence MSC phenotype and function in health and disease – including cellular, chemical and physical interactions. The most recent and relevant illustrative examples of novel bioengineering approaches to mimic biological, chemical, and mechanical microenvironmental signals present in the native MSC niche are summarized, with special emphasis on the forefront techniques to achieve bio-chemical complexity and dynamic cultures. In particular, the skeletal MSC niche and applications focusing on the bone regenerative potential of MSC are addressed. The aim of the review was to recognize the limitations of the current MSC niche in vitro models and to identify potential opportunities to fill the bridge between fundamental science and clinical application of MSCs. KW - Mesenchymal stem/stromal cells KW - skeletal progenitor cells KW - niche KW - in vitro models KW - bone KW - tissue engineering Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268823 SN - 1473-2262 VL - 37 ER - TY - JOUR A1 - Sponsler, Douglas A1 - Kallnik, Katharina A1 - Requier, Fabrice A1 - Classen, Alice A1 - Maihoff, A. Fabienne A1 - Sieger, Johanna A1 - Steffan-Dewenter, Ingolf T1 - Floral preferences of mountain bumble bees are constrained by functional traits but flexible through elevation and season JF - Oikos N2 - Patterns of resource use by animals can clarify how ecological communities have assembled in the past, how they currently function and how they are likely to respond to future perturbations. Bumble bees (Hymentoptera: Bombus spp.) and their floral hosts provide a diverse yet tractable system in which to explore resource selection in the context of plant–pollinator networks. Under conditions of resource limitation, the ability of bumble bees species to coexist should depend on dietary niche overlap. In this study, we report patterns and dynamics of floral morphotype preferences in a mountain bumble bee community based on ~13 000 observations of bumble bee floral visits recorded along a 1400 m elevation gradient. We found that bumble bees are highly selective generalists, rarely visiting floral morphotypes at the rates predicted by their relative abundances. Preferences also differed markedly across bumble bee species, and these differences were well-explained by variation in bumble bee tongue length, generating patterns of preference similarity that should be expected to predict competition under conditions of resource limitation. Within species, though, morphotype preferences varied by elevation and season, possibly representing adaptive flexibility in response to the high elevational and seasonal turnover of mountain floral communities. Patterns of resource partitioning among bumble bee communities may determine which species can coexist under the altered distributions of bumble bees and their floral hosts caused by climate and land use change. KW - resource selection KW - coexistence KW - competition KW - foraging KW - niche KW - pollinator Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259653 VL - 2022 IS - 3 ER -