分类: 生物学 >> 生物物理学 >> 免疫学 提交时间: 2016-05-15
摘要:The lineage commitment of HSCs generates balanced myeloid and lymphoid populations in hematopoiesis. However, the underlying mechanisms that control this process remain largely unknown. Here, we show that insulin-insulin receptor (InsR) signaling is required for lineage commitment of multipotent progenitors (MPPs). Deletion of Insr in murine bone marrow causes skewed differentiation of MPPs to myeloid cells. mTOR acts as a downstream effector that modulates MPP differentiation. mTOR activates Stat3 by phosphorylation at serine 727 under insulin stimulation, which binds to the promoter of Ikaros, leading to its transcription priming. Our findings reveal that the insulin-InsR signaling drives MPP differentiation into lymphoid lineages in early lymphopoiesis, which is essential for maintaining a balanced immune system for an individual organism.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要:Mesenchymal stem cells (MSCs) are a reliable cell source for tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. Here, we investigate HOXB7 function in the osteogenic differentiation potentials of MSCs using stem cells from apical papilla (SCAPs) and bone marrow stem cells (BMSCs). The HOXB7 gene is highly expressed in BMSCs compared with dental tissue-derived MSCs. We found that, in vitro, over-expression of HOXB7 in SCAPs enhanced alkaline phosphatase (ALP) activity and mineralization. HOXB7 over-expression affected the mRNA expression of osteonectin (ON), collagen alpha-2(I) chain (COL1A2), bone sialoprotein (BSP), and osteocalcin (OCN), led to the expression of the key transcription factor, runt-related transcription factor 2 (RUNX2), and promoted SCAP osteogenic differentiation in vitro. The knock-down of HOXB7 inhibited ALP activity, mineralization, and the expression of ON, BSP, COL1A2, OCN, and RUNX2 in BMSCs in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when HOXB7 was activated. Furthermore, Over-expression of HOXB7 significantly increased the levels of HOXB7 associated with the BSP promoter by ChIP assays. Taken together, these results indicate that HOXB7 enhances SCAP osteogenic differentiation by up-regulating RUNX2 and directly activating transcript of BSP. Thus, the activation of HOXB7 signaling might improve tissue regeneration mediated by MSCs. These results provide insight into the mechanism underlying the directed differentiation of MSCs.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-05
摘要:Chinese medicine, Fuzhenghuayu (FZHY), appears to prevent fibrosis progression and improve liver function in humans. Here we found that FZHY enhanced hepatocyte differentiation from human embryonic stem cells (hESC). After treatment with FZHY, albumin expression was consistently increased during differentiation and maturation process, and expression of metabolizing enzymes and transporter were also increased. Importantly, expression of mesenchymal cell and cholangiocyte marker was significantly reduced by treatment with FZHY, indicating that one possible mechanism of FZHY's role is to inhibit the formation of mesenchymal cells and cholangiocytes. Edu-labelled flow cytometric analysis showed that the percentage of the Edu positive cells was increased in the treated cells. These results indicate that the enhanced proliferation involved hepatocytes rather than another cell type. Our investigations further revealed that these enhancements by FZHY are mediated through activation of canonical Wnt and ERK pathways and inhibition of Notch pathway. Thus, FZHY not only promoted hepatocyte differentiation and maturation, but also enhanced hepatocyte proliferation. These results demonstrate that FZHY appears to represent an excellent therapeutic agent for the treatment of liver fibrosis, and that FZHY treatment can enhance our efforts to generate mature hepatocytes with proliferative capacity for cell-based therapeutics and for pharmacological and toxicological studies.
分类: 生物学 >> 植物学 >> 植物生态学和植物地理学 提交时间: 2016-05-04
Biochar management has been proposed as a possible tool to mitigate anthropogenic CO2 emissions, and thus far its impacts in forested environments remain poorly understood. We conducted a large-scale, replicated field experiment using 0.05-ha plots in the boreal region in northern Sweden to evaluate how soil and vegetation properties and processes responded to biochar application and the disturbance associated with burying biochar in the soil. We employed a randomized block design, where biochar and soil mixing treatments were established in factorial combination (i.e., control, soil mixing only, biochar only, and biochar and soil mixing; n = 6 plots of each). After two growing seasons, we found that biochar application enhanced net soil N mineralization rates and soil concentrations regardless of the soil mixing treatment, but had no impact on the availability of
, the majority of soil microbial community parameters, or soil respiration. Meanwhile, soil mixing enhanced soil
concentrations, but had negative impacts on net N mineralization rates and several soil microbial community variables. Many of the effects of soil mixing on soil nutrient and microbial community properties were less extreme when biochar was also added. Biochar addition had almost no effects on vegetation properties (except for a small reduction in species richness of the ground layer vegetation), while soil mixing caused significant reductions in graminoid and total ground layer vegetation cover, and enhanced seedling survival rates of P. sylvestris, and seed germination rates for four tree species. Our results suggest that biochar application can serve as an effective tool to store soil C in boreal forests while enhancing
availability. They also suggest that biochar may serve as a useful complement to site preparation techniques that are frequently used in the boreal region, by enhancing soil fertility and reducing nutrient losses when soils are scarified during site preparation.