Thanatotranscriptome genes actively expressed after organismal death, bioRxiv, 2016-06-11
AbstractA continuing enigma in the study of biological systems is what happens to highly ordered structures, far from equilibrium, when their regulatory systems suddenly become disabled. In life, genetic and epigenetic networks precisely coordinate the expression of genes -- but in death, it is not known if gene expression diminishes gradually or abruptly stops or if specific genes are involved. We investigated the unwinding of the clock by identifying upregulated genes, assessing their functions, and comparing their transcriptional profiles through postmortem time in two species, mouse and zebrafish. We found transcriptional abundance profiles of 1,063 genes were significantly changed after death of healthy adult animals in a time series spanning from life to 48 or 96 h postmortem. Ordination plots revealed non-random patterns in profiles by time. While most thanatotranscriptome (thanatos-, Greek defn. death) transcript levels increased within 0.5 h postmortem, some increased only at 24 and 48 h. Functional characterization of the most abundant transcripts revealed the following categories stress, immunity, inflammation, apoptosis, transport, development, epigenetic regulation, and cancer. The increase of transcript abundance was presumably due to thermodynamic and kinetic controls encountered such as the activation of epigenetic modification genes responsible for unraveling the nucleosomes, which enabled transcription of previously silenced genes (e.g., development genes). The fact that new molecules were synthesized at 48 to 96 h postmortem suggests sufficient energy and resources to maintain self-organizing processes. A step-wise shutdown occurs in organismal death that is manifested by the apparent upregulation of genes with various abundance maxima and durations. The results are of significance to transplantology and molecular biology.
biorxiv systems-biology 200-500-users 2016Massively parallel clonal analysis using CRISPRCas9 induced genetic scars, bioRxiv, 2016-06-02
A key goal of developmental biology is to understand how a single cell transforms into a full-grown organism consisting of many cells. Although impressive progress has been made in lineage tracing using imaging approaches, analysis of vertebrate lineage trees has mostly been limited to relatively small subsets of cells. Here we present scartrace, a strategy for massively parallel clonal analysis based on Cas9 induced genetic scars in the zebrafish.
biorxiv systems-biology 0-100-users 2016Revised estimates for the number of human and bacteria cells in the body, bioRxiv, 2016-01-07
We critically revisit the ″common knowledge″ that bacteria outnumber human cells by a ratio of at least 101 in the human body. We found the total number of bacteria in the ″reference man″ to be 3.9·1013, with an uncertainty (SEM) of 25%, and a variation over the population (CV) of 52%. For human cells we identify the dominant role of the hematopoietic lineage to the total count of body cells (≈90%), and revise past estimates to reach a total of 3.0·1013human cells in the 70 kg ″reference man″ with 2% uncertainty and 14% CV. Our analysis updates the widely-cited 101 ratio, showing that the number of bacteria in our bodies is actually of the same order as the number of human cells. Indeed, the numbers are similar enough that each defecation event may flip the ratio to favor human cells over bacteria.
biorxiv systems-biology 500+-users 2016