Dev120741 2840..2849
نویسندگان
چکیده
Much of development and disease concerns the generation of gene expression differences between related cells sharing similar niches. However, most analyses of gene expression only assess population and time-averaged levels of steady-state transcription. The mechanisms driving differentiation are buried within snapshots of the average cell, lacking dynamic information and the diverse regulatory history experienced by individual cells. Here, we use a quantitative imaging platform with large time series data sets to determine the regulation of developmental gene expression by cell cycle, lineage, motility and environment. We apply this technology to the regulation of the pluripotency gene Nanog in mouse embryonic stem cells. Our data reveal the diversity of cell and population-level interactions with Nanog dynamics and heterogeneity, and how this regulation responds to triggers of pluripotency. Cell cycles are highly heterogeneous and cycle time increases with Nanog reporter expression, with longer, more variable cycle times as cells approach ground-state pluripotency. Nanog reporter expression is highly stable over multiple cell generations, with fluctuations within cycles confined by an attractor state. Modelling reveals an environmental component to expression stability, in addition to any cell-autonomous behaviour, and we identify interactions of cell density with both cycle behaviour and Nanog. Rex1 expression dynamics showed shared and distinct regulatory effects. Overall, our observations of multiple partially overlapping dynamic heterogeneities imply complex cell and environmental regulation of pluripotent cell behaviour, and suggest simple deterministic views of stem cell states are inappropriate.
منابع مشابه
Insurance Coverage of Puberty Blocker Therapies for Transgender Youth.
Youth whose natural pubertal development would be detrimental to their psychological and general well-being can be treated with “puberty blockers” to prevent irreversible phenotypic changes. In our experience, the most effective medications are the gonadotropin-releasing hormone (GnRH) agonist leuprolide injections (Lupron; AbbVie, Chicago, IL) or histrelin subcutaneous implant (Supprelin, Vant...
متن کاملGeneralized Bullous Fixed Drug Eruption Following Metamizole (Re-)Exposure: A Medical Error-analytic Case Study.
متن کامل
Non-stationary component extraction in noisy multicomponent signal using polynomial chirping Fourier transform
Inspired by track-before-detection technology in radar, a novel time-frequency transform, namely polynomial chirping Fourier transform (PCFT), is exploited to extract components from noisy multicomponent signal. The PCFT combines advantages of Fourier transform and polynomial chirplet transform to accumulate component energy along a polynomial chirping curve in the time-frequency plane. The par...
متن کاملTraffic diversity and code coverage: a preliminary analysis
It is generally assumed that using more diverse traffic to test network devices could achieve larger code coverage. However, how to describe the diversity of traffic traces and the relationship between the traffic diversity and code coverage is still an issue. In this paper, the traffic diversity is defined using the number of packets and the size of the subnets involved, and traces having vari...
متن کاملLoss of NGF-TrkA signaling from the CNS is not sufficient to induce cognitive impairments in young adult or intermediate-aged mice.
Many molecules expressed in the CNS contribute to cognitive functions either by modulating neuronal activity or by mediating neuronal trophic support and/or connectivity. An ongoing discussion is whether signaling of nerve growth factor (NGF) through its high-affinity receptor TrkA contributes to attention behavior and/or learning and memory, based on its expression in relevant regions of the C...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2015