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  • 1
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    Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-03-25
    Description: Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility. Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482136/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482136/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adam, Rene C -- Yang, Hanseul -- Rockowitz, Shira -- Larsen, Samantha B -- Nikolova, Maria -- Oristian, Daniel S -- Polak, Lisa -- Kadaja, Meelis -- Asare, Amma -- Zheng, Deyou -- Fuchs, Elaine -- R01 AR031737/AR/NIAMS NIH HHS/ -- R01-AR31737/AR/NIAMS NIH HHS/ -- R21 MH099452/MH/NIMH NIH HHS/ -- R21MH099452/MH/NIMH NIH HHS/ -- T32 GM066699/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 May 21;521(7552):366-70. doi: 10.1038/nature14289. Epub 2015 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology &Development, The Rockefeller University, New York, New York 10065, USA. ; Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. ; 1] Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA [2] Departments of Neurology and Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25799994" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Adult Stem Cells/*cytology/metabolism ; Animals ; Base Sequence ; Cell Differentiation/*genetics ; Cell Lineage/*genetics ; Chromatin/genetics/metabolism ; Enhancer Elements, Genetic/*genetics ; Female ; Hair Follicle/*cytology ; Mice ; Organ Specificity ; SOX9 Transcription Factor/*metabolism ; Stem Cell Niche ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
    Electronic Resource
    Electronic Resource
    Human Semen Quality in Relation to Dietary Pesticide Exposure and Organic Diet (1999)
    Springer
    Archives of environmental contamination and toxicology 37 (1999), S. 415-423 
    Details
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract. The objective of the study was to corroborate or refute the hypothesis that farmers having a high intake of organic grown commodities have a high semen quality due to their expected lower level of dietary pesticides intake. Food frequency data and semen were collected from 256 farmers (171 traditional farmers and 85 organic farmers, overall participation rate: 32%) who were selected from central registers. Each farmer delivered one semen sample before the spraying season started. The farmers were divided into three groups where the commodities from organic production contributed no (N, 0%), medium (M, 1–49%), or a high (H, 50–100%) proportion of the fruit and vegetables consumed. Farmers having a high relative intake of organically grown fruit and vegetables also had a high relative consumption of organically produced meat, milk, and bread, and differences were observed comparing the actual mean intake of single commodities, such as rice, potato, and pork meat. The current individual dietary intake of 40 pesticides was estimated using food frequencies and generalized serving size data in combination with data on pesticide concentrations in food commodities as obtained from the National Danish Food Monitoring Program. The estimated pesticide intake was significantly lower among farmers of group H, but for all three groups of farmers the average dietary intake of 40 pesticides was at or below 1% of the acceptable daily intake (ADI) except for the dithiocarbamates (max = 0.21 μg/kg day = 2.2% ADI), methidathion, (max = 0.01 μg/kg day = 1.4% ADI), and 2-phenylphenol (max = 0.21 μg/kg day = 1.1% ADI). The median sperm concentration for the three groups of farmers was not significantly different (p = 0.40, median sperm concentration was N = 62, M = 44, and H = 75 million/ml). The group of men without organic food intake had a significant lower proportion of morphologically normal spermatozoa, but in relation to 14 other semen parameters no significant differences were found between the groups. Intake of 40 individual pesticides was correlated with four semen parameters (concentration, percentage dead spermatozoa, percentage normal sperm heads, and motility [VCL]). Five significant correlations (p value 0.01) were found among the 160 comparisons in relation to percentage dead spermatozoa: azinphos-methyl, carbaryl, chlorfenson, fenitrothion, and tetradifon. For all of them a lower percentage of dead spermatozoa were found in the groups with a high dietary intake of the specific pesticide. In contrast, for all pesticides evaluated only minor differences were found between the groups when considering spermatozoa concentration, morphology, and motility. In conclusion, the estimated dietary intake of 40 pesticides did not entail a risk of impaired semen quality, but precautions should be taken when generalizing this negative result to populations with a higher dietary exposure level or an intake of other groups of pesticides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002449900533
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    Paper (German National Licenses)
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  • 3
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    The genetic architecture of mitochondrial dysfunction in Parkinson’s disease (2018)
    Springer
    Details
    Publication Date: 2018-01-25
    Print ISSN: 0302-766X
    Electronic ISSN: 1432-0878
    Topics: Biology , Medicine
    Published by Springer
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  • 4
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    Constraining globular cluster formation through studies of young massive clusters - I. A lack of ongoing star formation within young clusters (2013)
    Oxford University Press
    Details
    Publication Date: 2013-11-17
    Description: We present a survey of 130 Galactic and extragalactic young massive clusters (YMCs, 10 4  〈  M /M  〈 10 8 , 10 〈  t /Myr 〈 1000) with integrated spectroscopy or resolved stellar photometry (40 presented here and 90 from the literature) and use the sample to search for evidence of ongoing star formation within the clusters. Such episodes of secondary (or continuous) star formation are predicted by models that attempt to explain the observed chemical and photometric anomalies observed in globular clusters as being due to the formation of a second stellar population within an existing first population. Additionally, studies that have claimed extended star formation histories within Large/Small Magellanic Cloud intermediate-age clusters (1–2 Gyr), also imply that many YMCs should show ongoing star formation. Based on visual inspection of the spectra and/or the colour–magnitude diagrams, we do not find evidence for ongoing star formation within any of the clusters, and use this to place constraints on the above models. Models of continuous star formation within clusters, lasting for hundreds of Myr, are ruled out at high significance (unless stellar initial mass function variations are invoked). Models for the (nearly instantaneous) formation of a secondary population within an existing first generation are not favoured, but are not formally discounted due to the finite sampling of age/mass-space.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 5
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    Human Semen Quality in Relation to Dietary Pesticide Exposure and Organic Diet (1999)
    Springer
    Details
    Publication Date: 1999-10-01
    Print ISSN: 0090-4341
    Electronic ISSN: 1432-0703
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Published by Springer
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