Systems Genetic Analysis of Osteoblast-Lineage Cells

The osteoblast-lineage consists of cells at various stages of maturation that are essential for skeletal development, growth, and maintenance. Over the past decade, many of the signaling cascades that regulate this lineage have been elucidated; however, little is known of the networks that coordinate, modulate, and transmit these signals. Here, we identify a gene network specific to the osteoblast-lineage through the reconstruction of a bone co-expression network using microarray profiles collected on 96 Hybrid Mouse Diversity Panel (HMDP) inbred strains. Of the 21 modules that comprised the bone network, module 9 (M9) contained genes that were highly correlated with prototypical osteoblast maker genes and were more highly expressed in osteoblasts relative to other bone cells. In addition, the M9 contained many of the key genes that define the osteoblast-lineage, which together suggested that it was specific to this lineage. To use the M9 to identify novel osteoblast genes and highlight its biological relevance, we knocked-down the expression of its two most connected “hub” genes, Maged1 and Pard6g. Their perturbation altered both osteoblast proliferation and differentiation. Furthermore, we demonstrated the mice deficient in Maged1 had decreased bone mineral density (BMD). It was also discovered that a local expression quantitative trait locus (eQTL) regulating the Wnt signaling antagonist Sfrp1 was a key driver of the M9. We also show that the M9 is associated with BMD in the HMDP and is enriched for genes implicated in the regulation of human BMD through genome-wide association studies. In conclusion, we have identified a physiologically relevant gene network and used it to discover novel genes and regulatory mechanisms involved in the function of osteoblast-lineage cells. Our results highlight the power of harnessing natural genetic variation to generate co-expression networks that can be used to gain insight into the function of specific cell-types

嗜盐嗜碱多能硫碱弧菌SOB306代谢工程及脱硫工艺研究

Abstract Background Infant feeding practices are known to influence the child’s long-term health. Studies have associated obesity and other diseases with reduced breastfeeding and early introduction of high calorie beverages (HCBs). The rising prevalence of obesity is already a problem in most developed countries, especially Australia, but cultural differences are influential. Our aim is to examine and compare infant feeding practices and educational levels of respondents through questionnaires in three culturally different sites: Campbelltown (South Western Sydney), Australia, Singapore and Ho Chi Minh City, Vietnam (HCMC). Methods Consenting parents and carers (aged ≥18 years old) of at least one child (≤6 years old) were recruited from paediatric clinics in Campbelltown, Singapore and HCMC. Participants completed an infant feeding practices questionnaire regarding breastfeeding, beverage and solid initiation in addition to the parent’s ethnicity, age, and educational level. Data was analysed quantitatively using SPSS. Results Two hundred eighty-three participants were recruited across the three sites, HCMC (n = 84), Campbelltown (n = 108), and Singapore (n = 91). 237 (82.6%) children were breastfed but in all only 100 (60.2%) were exclusively breastfed for five months or more. There was a statistical difference in rates of breast feeding between each region. HCMC (n = 18, 21.4%) had the lowest, followed by Campbelltown (n = 35, 32.4%), and then Singapore (n = 47, 51.7%). There was also a difference in rates of introduction of HCBs by 3 years of age, with those in HCMC (n = 71, 84.5%) were higher than Campbelltown (n = 71, 65.8%) and Singapore (n = 48, 52.8%). The educational level of respondents was lower in Vietnam where only 46.4% (n = 39) had completed post-secondary education, compared to 75.0% (n = 81) in Campbelltown and 75.8% (n = 69) in Singapore. Conclusions Rates of breast feeding were inversely correlated with rates of introduction of HCB and positively related to educational achievement. Vietnam had lowest rates of breast feeding, higher rates of introduction of HCBs, and lower rates of education. Given rising rates of obesity, there is a need for more effective programmes to promote breast feeding and restrict false advertising of HCBs