Linking single-cell measurements of mass, growth rate, and gene expression

Kimmerling, Robert J.; Prakadan, Sanjay M.; Gupta, Apoorv; Calistri, Nicholas L.; Stevens, Mark M.; Ölçüm, Selim; Cermak, Nathan; Drake, Riley S.; Pelton, Kristine; Smet, Frederik De; Ligon, Keith L.; Shalek, Alex K.; Manalis, Scott R.

doi:10.1186/s13059-018-1576-0

Cited by 47 publications

(33 citation statements)

References 58 publications

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“…Increasing the accuracy and throughput in producing single-cell growth curves will be crucial in this respect. The parallelization of a technique involving suspended microchannel resonators now allows high-throughput measurement of buoyant cell mass 113 , together with single-cell RNA sequencing 114 . Other approaches aiming at simplifying the experimental set-up are also promising 115,116 .…”

Section: A Deeper View Of Single-cell Growthmentioning

confidence: 99%

The physics of cell-size regulation across timescales

et al. 2019

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Section: A Deeper View Of Single-cell Growthmentioning

confidence: 99%

The physics of cell-size regulation across timescales

et al. 2019

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“…Density independent (DI) effects include intrinsic growth rate, which measures the capacity of a cell line to grow exponentially under ideal conditions. In cell biology, these (DD and DI) are often used as indicators of cell fitness 17 – 19 . This, however, ignores the FD interactions, which often determine competitive outcomes.…”

Section: Introductionmentioning

confidence: 99%

Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines

Freischel

Damaghi

Cunningham

et al. 2021

Sci Rep

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Tumors are highly dynamic ecosystems in which diverse cancer cell subpopulations compete for space and resources. These complex, often non-linear interactions govern continuous spatial and temporal changes in the size and phenotypic properties of these subpopulations. Because intra-tumoral blood flow is often chaotic, competition for resources may be a critical selection factor in progression and prognosis. Here, we quantify resource competition using 3D spheroid cultures with MDA-MB-231 and MCF-7 breast cancer cells. We hypothesized that MCF-7 cells, which primarily rely on efficient aerobic glucose metabolism, would dominate the population under normal pH and low glucose conditions; and MDA-MB-231 cells, which exhibit high levels of glycolytic metabolism, would dominate under low pH and high glucose conditions. In spheroids with single populations, MCF-7 cells exhibited equal or superior intrinsic growth rates (density-independent measure of success) and carrying capacities (density-dependent measure of success) when compared to MDA-MB-231 cells under all pH and nutrient conditions. Despite these advantages, when grown together, MCF-7 cells do not always outcompete MDA-MB-231 cells. MDA-MB-231 cells outcompete MCF-7 cells in low glucose conditions and coexistence is achieved in low pH conditions. Under all conditions, MDA-MB-231 has a stronger competitive effect (frequency-dependent interaction) on MCF-7 cells than vice-versa. This, and the inability of growth rate or carrying capacity when grown individually to predict the outcome of competition, suggests a reliance on frequency-dependent interactions and the need for competition assays. We frame these results in a game-theoretic (frequency-dependent) model of cancer cell interactions and conclude that competition assays can demonstrate critical density-independent, density-dependent and frequency-dependent interactions that likely contribute to in vivo outcomes.

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“…CTC and primary tumor samples in TCL supplemented with 1% (v/v) 2-mercaptoethanol buffer were processed through Smart-Seq2 as previously described 37,51 . Briefly, cellular nucleic acids from each lysed single cell were extracted from TCL lysis buffer using a 2.2x (v/v) RNA SPRI (RNA-clean AMPure beads, Beckman-Coulter).…”

Section: Methodsmentioning

confidence: 99%

Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

Hamza

Miller

Meier

et al. 2020

Preprint

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Existing pre-clinical methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) en route to forming metastases have not been capable of providing a direct measure of CTC intravasation rate and subsequent half-life in the circulation. Here, we demonstrate an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood over several hours between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts. By tracking CTC transfer rates using an autochthonous small cell lung cancer model, we extrapolated half-life times in the circulation of 50-100 seconds and intravasation rates between 4,000 and 27,000 CTCs/hour − an average daily shedding rate equivalent to ~0.07% of the total number of primary tumor cells in the lung. Additionally, transfer of 1-2% of daily-shed CTCs from late-stage tumor-bearing mice generated macrometastases in healthy recipient mice. We envision that our technique will help further elucidate the role of CTCs and the rate-limiting steps in metastasis

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Linking single-cell measurements of mass, growth rate, and gene expression

Cited by 47 publications

References 58 publications

The physics of cell-size regulation across timescales

The physics of cell-size regulation across timescales

Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines

Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

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