scholarly journals Sphingolipid Control of Fibroblast Heterogeneity Revealed by Single-Cell Lipidomics

2021 ◽  
Author(s):  
Laura Capolupo ◽  
Irina Khven ◽  
Luigi Mazzeo ◽  
Galina Glousker ◽  
Francesco Russo ◽  
...  

Human cells produce thousands of lipids that impact a wide range of biological processes in ways we are only starting to characterize. The cellular composition in lipids changes during differentiation events and also varies across individual cells of the same type. Yet, the precise differences in lipid composition that directly affect cell phenotypes remain unknown. Here we have measured the lipidomes and transcriptomes of individual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging to single-cell transcriptomics. We found that the cell-to-cell variation of specific lipid metabolic pathways contributes to the establishment of cell states involved in wound repair and in skin cancer growth. Sphingolipid composition defined fibroblast subpopulations while sphingolipid metabolic rewiring drove cell state transitions. These data uncover a role for cell-to-cell lipid heterogeneity in the determination of cell states and reveal a new regulatory component to the homeostasis and self-organization of multicellular systems.

2018 ◽  
Author(s):  
Anastasiya Moskalyuk ◽  
R. Frank Kooy ◽  
Michele Giugliano

AbstractThe Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of co-morbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signalling, and an altered balance between excitation and inhibition has been hypothesised to underlie the clinical consequences of absence of the protein. Using FMRP knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best predicts our experimental observations during the ex vivo formation of the network connections.


2020 ◽  
Vol 86 (8) ◽  
pp. 23-31
Author(s):  
V. G. Amelin ◽  
D. S. Bolshakov

The goal of the study is developing a methodology for determination of the residual amounts of quaternary ammonium compounds (QAC) in food products by UHPLC/high-resolution mass spectrometry after water-acetonitrile extraction of the determined components from the analyzed samples. The identification and determination of QAC was carried out on an «UltiMate 3000» ultra-high-performance liquid chromatograph (Thermo Scientific, USA) equipped with a «maXis 4G» high-resolution quadrupole-time-of-flight mass spectrometric detector and an ion spray «ionBooster» source (Bruker Daltonics, Germany). Samples of milk, cheese (upper cortical layer), dumplings, pork, chicken skin and ground beef were used as working samples. Optimal conditions are specified for chromatographic separation of the mixture of five QAC, two of them being a mixture of homologues with a linear structure (including isomeric forms). The identification of QAC is carried out by the retention time, exact mass of the ions, and coincidence of the mSigma isotopic distribution. The limits for QAC detection are 0.1 – 0.5 ng/ml, the determination limits are 1 ng/ml for aqueous standard solutions. The determinable content of QAC in food products ranges within 1 – 100 ng/g. The results of analysis revealed the residual amount of QAC present in all samples, which confirms data of numerous sources of information about active use of QAC-based disinfectants in the meat and dairy industry. The correctness of the obtained results is verified by introduction of the additives in food products at a level of 10 ng/g for each QAC. The relative standard deviation of the analysis results does not exceed 0.18. The duration of the analysis is 30 – 40 min.


2017 ◽  
Vol 15 (1) ◽  
pp. 21
Author(s):  
Haryo Suganda ◽  
Raja Muhammad Amin

This study is motivated the identification of policies issued by the regional Governmentof Rokan Hulu in the form of Regulatory region number 1 by 2015 on the determination of thevillage and Indigenous Village. Political dynamics based on various interests against themanufacture of, and decision-making in the process of formation of the corresponding localregulations determination of Indigenous Villages in the Rokan Hulu is impacted to a verysignificantamount of changes from the initial draft of the number i.e. 21 (twenty one) the villagebecame Customary 89 (eighty-nine) the Indigenous Villages who have passed. Type of thisresearch is a qualitative descriptive data analysis techniques. The research aims to describe theState of the real situation in a systematic and accurate fact analysis unit or related research, aswell as observations of the field based on the data (information). Method of data collectionwas done with interviews, documentation, and observations through fieldwork (field research).The results of the research on the process of discussion of the draft local regulations andmutual agreement about Designation of Indigenous Villages in the Rokan Hulu is, showed thatthe political dynamics that occur due to the presence of various political interests, rejectionorally by Villagers who were judged to have met the requirements of Draft Regulations to beformulated and the area for the set to be Indigenous Villages, and also there is a desire fromsome villages in the yet to Draft local regulations in order to set the Indigenous village , there isa wide range of interests of these aspects influenced the agreement to assign the entire localVillage which is in the Rokan Hulu become Indigenous village, and the village of Transmigrationinto administrative Villages where the initiator of the changes in the number of IndigenousVillages in the Rokan Hulu it is the desire of the local Government of its own.


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