Design and fabrication of high-throughput application-specific microfluidic devices for studying single-cell responses to extracellular perturbations

Author(s):  
Amin A. Banaeiyan ◽  
Doryaneh Ahmadpour ◽  
Caroline B. Adiels ◽  
Mattias Goksör
PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100042 ◽  
Author(s):  
Matthew M. Crane ◽  
Ivan B. N. Clark ◽  
Elco Bakker ◽  
Stewart Smith ◽  
Peter S. Swain

2001 ◽  
Vol 138 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Takuji Kasamatsu ◽  
Uri Polat ◽  
Anthony Norcia ◽  
Mark Pettet

1980 ◽  
Vol 89 (2) ◽  
pp. 176-179 ◽  
Author(s):  
Nathan B. Gross ◽  
Wladimiro S. Lifschitz

Single cell data were obtained from the inferior colliculus of normal gerbils and from those treated with ethacrynic acid. Response changes found for the drug-treated animals are as follows: Fewer cells responded to auditory stimulation. Recruitment-like functions were found which were characterized by high threshold and precipitous increase in discharge rate with intensity. Some units showed abnormally low discharge rate over an extended intensity range, which could be the underlying change in responsiveness in human patients with reduced loudness range. One half as many collicular units were responsive to auditory phase differences. The most severely affected ears showed abnormal dependency upon phase relations. This would affect auditory space perception.


2019 ◽  
Author(s):  
Hiraku Miyagi ◽  
Michio Hiroshima ◽  
Yasushi Sako

AbstractGrowth factors regulate cell fates, including their proliferation, differentiation, survival, and death, according to the cell type. Even when the response to a specific growth factor is deterministic for collective cell behavior, significant levels of fluctuation are often observed between single cells. Statistical analyses of single-cell responses provide insights into the mechanism of cell fate decisions but very little is known about the distributions of the internal states of cells responding to growth factors. Using multi-color immunofluorescent staining, we have here detected the phosphorylation of seven elements in the early response of the ERBB–RAS–MAPK system to two growth factors. Among these seven elements, five were analyzed simultaneously in distinct combinations in the same single cells. Although principle component analysis suggested cell-type and input specific phosphorylation patterns, cell-to-cell fluctuation was large. Mutual information analysis suggested that cells use multitrack (bush-like) signal transduction pathways under conditions in which clear cell fate changes have been reported. The clustering of single-cell response patterns indicated that the fate change in a cell population correlates with the large entropy of the response, suggesting a bet-hedging strategy is used in decision making. A comparison of true and randomized datasets further indicated that this large variation is not produced by simple reaction noise, but is defined by the properties of the signal-processing network.Author SummaryHow extracellular signals, such as growth factors (GFs), induce fate changes in biological cells is still not fully understood. Some GFs induce cell proliferation and others induce differentiation by stimulating a common reaction network. Although the response to each GF is reproducible for a cell population, not all single cells respond similarly. The question that arises is whether a certain GF conducts all the responding cells in the same direction during a fate change, or if it initially stimulates a variety of behaviors among single cells, from which the cells that move in the appropriate direction are later selected. Our current statistical analysis of single-cell responses suggests that the latter process, which is called a bet-hedging mechanism is plausible. The complex pathways of signal transmission seem to be responsible for this bet-hedging.


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