TY - JOUR
T1 - Simultaneous multiparameter cellular energy metabolism profiling of small populations of cells
AU - Kelbauskas, Laimonas
AU - Ashili, Shashaanka P.
AU - Lee, Kristen B.
AU - Zhu, Haixin
AU - Tian, Yanqing
AU - Meldrum, Deirdre
N1 - Funding Information:
The authors would like to thank the staff of the Center for Solid State Electronics Research at Arizona State University for their technical insights and assistance throughout the development of the microfabrication process. This work was supported by a grant from the NIH National Human Genome Research Institute, Centers of Excellence in Genomic Science (Grant No. 5 P50 HG002360, to DRM). The authors would like to thank Patti Senechal and Nana Hansen for the cell culture, Jeff Houkal, Dean Smith and Juan Vela for providing support with the systems integration, and Jordan Yaron for stimulating discussions on cancer cell biology.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Functional and genomic heterogeneity of individual cells are central players in a broad spectrum of normal and disease states. Our knowledge about the role of cellular heterogeneity in tissue and organism function remains limited due to analytical challenges one encounters when performing single cell studies in the context of cell-cell interactions. Information based on bulk samples represents ensemble averages over populations of cells, while data generated from isolated single cells do not account for intercellular interactions. We describe a new technology and demonstrate two important advantages over existing technologies: First, it enables multiparameter energy metabolism profiling of small cell populations (<100 cells)-A sample size that is at least an order of magnitude smaller than other, commercially available technologies; second, it can perform simultaneous real-time measurements of oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and mitochondrial membrane potential (MMP)-A capability not offered by any other commercially available technology. Our results revealed substantial diversity in response kinetics of the three analytes in dysplastic human epithelial esophageal cells and suggest the existence of varying cellular energy metabolism profiles and their kinetics among small populations of cells. The technology represents a powerful analytical tool for multiparameter studies of cellular function.
AB - Functional and genomic heterogeneity of individual cells are central players in a broad spectrum of normal and disease states. Our knowledge about the role of cellular heterogeneity in tissue and organism function remains limited due to analytical challenges one encounters when performing single cell studies in the context of cell-cell interactions. Information based on bulk samples represents ensemble averages over populations of cells, while data generated from isolated single cells do not account for intercellular interactions. We describe a new technology and demonstrate two important advantages over existing technologies: First, it enables multiparameter energy metabolism profiling of small cell populations (<100 cells)-A sample size that is at least an order of magnitude smaller than other, commercially available technologies; second, it can perform simultaneous real-time measurements of oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and mitochondrial membrane potential (MMP)-A capability not offered by any other commercially available technology. Our results revealed substantial diversity in response kinetics of the three analytes in dysplastic human epithelial esophageal cells and suggest the existence of varying cellular energy metabolism profiles and their kinetics among small populations of cells. The technology represents a powerful analytical tool for multiparameter studies of cellular function.
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U2 - 10.1038/s41598-018-22599-w
DO - 10.1038/s41598-018-22599-w
M3 - Article
C2 - 29531352
AN - SCOPUS:85044177651
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 4359
ER -