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Differential variability and correlation of gene expression identifies key genes involved in neuronal differentiation.

ABSTRACT: Understanding the dynamics of stem cell differentiation processes at the molecular level is a central challenge in developmental biology and regenerative medicine. Although the dynamic behaviors of differentiation regulators have been partially characterized, the architecture regulating the underlying molecular systems remains unclear.System-level analysis of transcriptional data was performed to characterize the dynamics of molecular networks in neural differentiation of stem cells. Expression of a network module of genes tightly co-expressed in mouse embryonic stem (ES) cells fluctuated greatly among cell populations before differentiation, but became stable following neural differentiation. During the neural differentiation process, genes exhibiting both differential variance and differential correlation between undifferentiated and differentiating states were related to developmental functions such as body axis development, neuronal movement, and transcriptional regulation. Furthermore, these genes were genetically associated with neuronal differentiation, providing support for the idea they are not only differentiation markers but could also play important roles in neural differentiation. Comparisons with transcriptional data from human induced pluripotent stem (iPS) cells revealed that the system of genes dynamically regulated during neural differentiation is conserved between mouse and human.The results of this study provide a systematic analytical framework for identifying key genes involved in neural differentiation by detecting their dynamical behaviors, as well as a basis for understanding the dynamic molecular mechanisms underlying the processes of neural differentiation.

SUBMITTER: Ando T

PROVIDER: S-EPMC4653947 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Differential variability and correlation of gene expression identifies key genes involved in neuronal differentiation.

Ando Tatsuya T Kato Ryuji R Honda Hiroyuki H

BMC systems biology 20151119

<h4>Background</h4>Understanding the dynamics of stem cell differentiation processes at the molecular level is a central challenge in developmental biology and regenerative medicine. Although the dynamic behaviors of differentiation regulators have been partially characterized, the architecture regulating the underlying molecular systems remains unclear.<h4>Result</h4>System-level analysis of transcriptional data was performed to characterize the dynamics of molecular networks in neural differen ...[more]

PMID: 26586157

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Project description:BACKGROUND:Exploration of the bioactive components of bovine milk has gained global interest due to their potential applications in human nutrition and health promotion. Despite advances in proteomics profiling, limited studies have been carried out to fully characterize the bovine milk proteome. This study explored the milk proteome of Jersey and Kashmiri cattle at day 90 of lactation using high-resolution mass spectrometry based quantitative proteomics nano-scale LC-MS/Q-TOF technique. Data are available via ProteomeXchange with identifier PXD017412. RESULTS:Proteins from whey were fractionated by precipitation into high and low abundant proteins. A total of 81 high-abundant and 99 low-abundant proteins were significantly differentially expressed between Kashmiri and Jersey cattle, clearly differentiating the two breeds at the proteome level. Among the top differentiating proteins, the Kashmiri cattle milk proteome was characterised by increased concentrations of immune-related proteins (apelin, acid glycoprotein, CD14 antigen), neonatal developmental protein (probetacellulin), xenobiotic metabolising enzyme (flavin monooxygenase 3 (FMO3), GLYCAM1 and HSP90AA1 (chaperone) while the Jersey milk proteome presented higher concentrations of enzyme modulators (SERPINA1, RAC1, serine peptidase inhibitor) and hydrolases (LTF, LPL, CYM, PNLIPRP2). Pathway analysis in Kashmiri cattle revealed enrichment of key pathways involved in the regulation of mammary gland development like Wnt signalling pathway, EGF receptor signalling pathway and FGF signalling pathway while a pathway (T-cell activation pathway) associated with immune system regulation was significantly enriched in Jersey cattle. Most importantly, the high-abundant FMO3 enzyme with an observed 17-fold higher expression in Kashmiri cattle milk seems to be a characteristic feature of the breed. The presence of this (FMO3) bioactive peptide/enzyme in Kashmiri cattle could be economically advantageous for milk products from Kashmiri cattle. CONCLUSION:In conclusion, this is the first study to provide insights not only into the milk proteome differences between Kashmiri and Jersey cattle but also provides potential directions for application of specific milk proteins from Kashmiri cattle in special milk preparations like infant formula.

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Differential variability and correlation of gene expression identifies key genes involved in neuronal differentiation.

Publications

Differential variability and correlation of gene expression identifies key genes involved in neuronal differentiation.

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