Fig 1.
Experiment overview and expression patterns.
A) Mouse and human pluripotent stems cells were exposed to neural differentiation factors to initiate differentiation and then sampled for RNA-sequencing every 4 or 10 minutes for the first 600 minutes. Expression trends along the time course for each gene were fit using a breakpoint model. B) Expression trends are shown for representative genes having patterns classified as not dynamic, immediate dynamic, or delayed dynamic. Immediate dynamic genes had an immediate up- or downregulation segment, whereas delayed dynamic genes had a flat initial segment. Trends were further characterized as having a peak, dip, or as cyclic (multiple peak/dip) (Methods).
Fig 2.
Initial human and mouse ortholog expression trends begin at similar times yet last for longer in human.
A) The number of genes having an up or down trend occurring immediately versus those displaying a delayed trend is shown. The two mouse/human bars represent genes having either immediate or delayed dynamics. The 99% confidence interval for the difference in the percent (ΔP%) of orthologs having an immediate up/down trend was -5.35% to -0.22%. B) The number of orthologs that had monotonic expression patterns (i.e. no breakpoints) along the time courses. The 99% confidence interval for the difference in the percent (ΔP%) of monotonic orthologs in human versus mouse was 23.98% to 32.98%. C) For non-monotonic genes (i.e. those having at least one breakpoint), histograms of the first breakpoint time are shown for mouse and human genes. D) Similar to C), the time of the first breakpoint is highlighted in either blue or red for mouse and human orthologs. E) The first breakpoint times for mouse and human orthologs are represented as smoothed densities (bean plots) with overlaid raw data, the median, and a box representing the interquartile range. The 99% confidence interval on the paired Wilcoxon rank sum statistic for shift in distribution (ΔM) was 157 to 196 minutes.
Fig 3.
Dynamic genes in either mouse or human experiments also display earlier breakpoints in mouse compared to human cells.
(A) The distribution of all breakpoint times among 3721 dynamic genes in Mouse and 4332 dynamic genes in Human. The values indicate the number of breakpoints occurring prior to 60 minutes, 100 minutes, and 250 minutes. Some genes may have multiple breakpoints in each time-frame. B) Smoothed density plot as previously described are shown for all breakpoint times among mouse and human dynamic genes. The 99% confidence interval for the Wilcoxon rank sum statistic shift in distribution (ΔM) for breakpoint times in human versus mouse was 154 to 172 minutes. C) The percent of genes having an up or down trend immediately versus those displaying a delayed trend (a period of stable expression for five consecutive time-points in mouse cells or three consecutive time-points in human cells followed by an up or down response). The 99% confidence interval for the difference in the percent (ΔP%) of genes having an immediate up/down trend was -3.89% to -0.89%. D) The number of genes that had monotonic expression patterns (i.e. no breakpoints) along the time course trending either up or down. The 99% confidence interval for the difference in the percent (ΔP%) of monotonic genes was 25.5% to 30.9%.
Fig 4.
Gene peaks occur earlier in mouse compared to human cells.
(A) The sorted peak time of ortholog genes highlighted in either blue or red for mouse and human orthologs, respectively. B) Histogram of the peak time for orthologs. The 99% confidence interval on the paired Wilcoxon rank sum statistic for shift in distribution (ΔM) was 220 to 254 minutes. C) Scatter plots of scaled normalized expression for the first four peaking orthologs (first in mouse) are shown with the breakpoint model fit from Trendy overlaid. The peak time is shown as a green dotted line. D) Histogram of the peak time for genes having a peak in either species. The 99% confidence interval on the Wilcoxon rank sum statistic for shift in distribution (ΔM) was 222 to 254 minutes. E) Scatter plots of scaled normalized expression for four peaking, immediate-early orthologs are shown with the breakpoint model fit overlaid and peak times indicated by the green dotted lines.
Fig 5.
Immediate versus delayed dynamics are similar between mouse and human genes having a peak or upregulation.
A) The number of ortholog peaks having the up trend starting immediately versus delayed in mouse and human. B) The percentage of all dynamic genes having an immediate peak in either mouse or human. C) Similar in structure to (A) for the number of orthologs having an having an immediate up trend. This broader categorization does include peaks. D) Similar in structure as (B) for all genes having upregulation in either mouse or human time courses.
Fig 6.
Rate of upregulation of gene expression is faster in mouse compared to human cells.
A) For orthologs having a peak in both mouse and human cells, the slopes of the up trend (left) and down trends (right) of the peak are shown as smoothed densities (bean plots) with overlaid raw data, the median, and a box representing the interquartile range. B) Similar as (A) for all genes having a peak in either mouse or human cells. C) For all orthologs having an immediate up trend, the slope of the first breakpoint is shown in a smoothed density plot (left). For genes having an immediate down trend, the slope of the first breakpoint is shown (right).