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The volumes and transcript counts of single cells reveal concentration homeostasis and capture biological noise.

Kempe H, Schwabe A, Crémazy F, Verschure PJ, Bruggeman FJ - Mol. Biol. Cell (2014)

Bottom Line: We compared three cell clones that differ only in the genomic integration site of an identical constitutively expressed reporter gene.We found that the cell-to-cell variability in the mRNA concentration is almost exclusively due to cell-to-cell variation in gene expression activity, whereas the cell-to-cell variation in mRNA number is larger, due to a significant contribution of cell volume variability.We concluded that the precise relationship between transcript number and cell volume sets the biological stochasticity of living cells.

View Article: PubMed Central - PubMed

Affiliation: Synthetic Systems Biology and Nuclear Organization Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.

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The theoretical and experimental relations between mRNA concentration and mRNA number noise and their dependency on volume. (A) Overview of theoretical relation used to analyze the data. The mRNA number noise  and mRNA concentration noise  can be decomposed into two terms; the volume-dependent noise  and gene-expression noise  (see Eq. 1). When there is homeostasis of mRNA concentration, the relation between  and  depends on the scaling of the variance in the conditional mRNA numbers. Under these conditions, the volume-dependent noise in mRNA numbers  equals the noise in the volume distribution . (B) Experimental data of the relation shown in the theoretical section (A). The different colors give the corresponding measures for the three different clones. The circle graphs show how the total mRNA number and mRNA concentration noise are decomposed. mRNA number noise is higher than concentration noise, mainly due to its volume contribution. The scaling of var(m/V) with volume for clone III is shown. The observed scaling is linear or quadratic, resulting in a deviation of ± 4% between  and . The scaling of var(m/V) with volume for clones I and II can be found in Supplemental Figure S10.
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Figure 4: The theoretical and experimental relations between mRNA concentration and mRNA number noise and their dependency on volume. (A) Overview of theoretical relation used to analyze the data. The mRNA number noise and mRNA concentration noise can be decomposed into two terms; the volume-dependent noise and gene-expression noise (see Eq. 1). When there is homeostasis of mRNA concentration, the relation between and depends on the scaling of the variance in the conditional mRNA numbers. Under these conditions, the volume-dependent noise in mRNA numbers equals the noise in the volume distribution . (B) Experimental data of the relation shown in the theoretical section (A). The different colors give the corresponding measures for the three different clones. The circle graphs show how the total mRNA number and mRNA concentration noise are decomposed. mRNA number noise is higher than concentration noise, mainly due to its volume contribution. The scaling of var(m/V) with volume for clone III is shown. The observed scaling is linear or quadratic, resulting in a deviation of ± 4% between and . The scaling of var(m/V) with volume for clones I and II can be found in Supplemental Figure S10.

Mentions: Figure 4B makes the same decomposition for the experimental data. It shows that the gene expression noise term accounts for ∼70% of the mRNA number noise and for greater than 95% of the mRNA concentration noise. This indicates that mRNA number noise has a large contribution that derives from the scaling of the number of transcripts per cell with the cell volume.


The volumes and transcript counts of single cells reveal concentration homeostasis and capture biological noise.

Kempe H, Schwabe A, Crémazy F, Verschure PJ, Bruggeman FJ - Mol. Biol. Cell (2014)

The theoretical and experimental relations between mRNA concentration and mRNA number noise and their dependency on volume. (A) Overview of theoretical relation used to analyze the data. The mRNA number noise  and mRNA concentration noise  can be decomposed into two terms; the volume-dependent noise  and gene-expression noise  (see Eq. 1). When there is homeostasis of mRNA concentration, the relation between  and  depends on the scaling of the variance in the conditional mRNA numbers. Under these conditions, the volume-dependent noise in mRNA numbers  equals the noise in the volume distribution . (B) Experimental data of the relation shown in the theoretical section (A). The different colors give the corresponding measures for the three different clones. The circle graphs show how the total mRNA number and mRNA concentration noise are decomposed. mRNA number noise is higher than concentration noise, mainly due to its volume contribution. The scaling of var(m/V) with volume for clone III is shown. The observed scaling is linear or quadratic, resulting in a deviation of ± 4% between  and . The scaling of var(m/V) with volume for clones I and II can be found in Supplemental Figure S10.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 4: The theoretical and experimental relations between mRNA concentration and mRNA number noise and their dependency on volume. (A) Overview of theoretical relation used to analyze the data. The mRNA number noise and mRNA concentration noise can be decomposed into two terms; the volume-dependent noise and gene-expression noise (see Eq. 1). When there is homeostasis of mRNA concentration, the relation between and depends on the scaling of the variance in the conditional mRNA numbers. Under these conditions, the volume-dependent noise in mRNA numbers equals the noise in the volume distribution . (B) Experimental data of the relation shown in the theoretical section (A). The different colors give the corresponding measures for the three different clones. The circle graphs show how the total mRNA number and mRNA concentration noise are decomposed. mRNA number noise is higher than concentration noise, mainly due to its volume contribution. The scaling of var(m/V) with volume for clone III is shown. The observed scaling is linear or quadratic, resulting in a deviation of ± 4% between and . The scaling of var(m/V) with volume for clones I and II can be found in Supplemental Figure S10.
Mentions: Figure 4B makes the same decomposition for the experimental data. It shows that the gene expression noise term accounts for ∼70% of the mRNA number noise and for greater than 95% of the mRNA concentration noise. This indicates that mRNA number noise has a large contribution that derives from the scaling of the number of transcripts per cell with the cell volume.

Bottom Line: We compared three cell clones that differ only in the genomic integration site of an identical constitutively expressed reporter gene.We found that the cell-to-cell variability in the mRNA concentration is almost exclusively due to cell-to-cell variation in gene expression activity, whereas the cell-to-cell variation in mRNA number is larger, due to a significant contribution of cell volume variability.We concluded that the precise relationship between transcript number and cell volume sets the biological stochasticity of living cells.

View Article: PubMed Central - PubMed

Affiliation: Synthetic Systems Biology and Nuclear Organization Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.

Show MeSH