Cell Cycle and Cell Size Dependent Gene Expression Reveals Distinct Subpopulations at Single-Cell Level

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Dolatabadi, SoheilaGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology (author)

Cell Cycle and Cell Size Dependent Gene Expression Reveals Distinct Subpopulations at Single-Cell Level

Article/chapterEnglish2017

Publisher, publication year, extent ...

2017-01-25
Frontiers Media SA,2017

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LIBRIS-ID:oai:gup.ub.gu.se/254812
https://gup.ub.gu.se/publication/254812URI
https://doi.org/10.3389/fgene.2017.00001DOI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Cell proliferation includes a series of events that is tightly regulated by several checkpoints and layers of control mechanisms. Most studies have been performed on large cell populations, but detailed understanding of cell dynamics and heterogeneity requires single-cell analysis. Here, we used quantitative real-time PCR, profiling the expression of 93 genes in single-cells from three different cell lines. Individual unsynchronized cells from three different cell lines were collected in different cell cycle phases (GO/G1 - S - G2/M) with variable cell sizes. We found that the total transcript level per cell and the expression of most individual genes correlated with progression through the cell cycle, but not with cell size. By applying the random forests algorithm, a supervised machine learning approach, we show how a multi-gene signature that classifies individual cells into their correct cell cycle phase and cell size can be generated. To identify the most predictive genes we used a variable selection strategy. Detailed analysis of cell cycle predictive genes allowed us to define subpopulations with distinct gene expression profiles and to calculate a cell cycle index that illustrates the transition of cells between cell cycle phases. In conclusion, we provide useful experimental approaches and bioinformatics to identify informative and predictive genes at the single-cell level, which opens up new means to describe and understand cell proliferation and subpopulation dynamics.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology hsv//eng
cell cycle
cell size
single-cell gene expression
machine learning
variable selection
random forests
cell subpopulations
cell transitions
mammalian-cells
transcription
breast
roles
dna
Genetics & Heredity

Added entries (persons, corporate bodies, meetings, titles ...)

Candia, J. (author)
Akrap, NinaGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xakrni (author)
Vannas, ChristofferGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xvanch (author)
Tomic, Tajana TesanGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xtesta (author)
Losert, W. (author)
Landberg, Göran,1963Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xlgora (author)
Åman, Pierre,1953Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xamapi (author)
Ståhlberg, Anders,1975Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology(Swepub:gu)xsandw (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för patologi (creator_code:org_t)

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