@article {Veloso016840, author = {Felipe A. Veloso}, title = {A general theory of differentiated multicellularity}, elocation-id = {016840}, year = {2015}, doi = {10.1101/016840}, publisher = {Cold Spring Harbor Laboratory}, abstract = {There is wide scientific consensus on the relevance of changes in the levels of gene expression for the cell differentiation process. Furthermore, research in the field has customarily assumed that such changes regulate this process when they interconnect in space and time by means of complex epigenetic mechanisms. Nevertheless, this assumed regulatory power lacks a clear definition and may even lead to logical inconsistencies. To tackle this problem, I analyzed publicly available high-throughput data of histone H3 post-translational modifications and mRNA abundance for different Homo sapiens, Mus musculus, and Drosophila melanogaster cell samples. Comprising genomic regions adjacent to transcription start sites, this analysis generated for each cell dataset a profile from pairwise partial correlations between histone modifications controlling for the respective mRNA levels. Here I report that these profiles, while explicitly uncorrelated to transcript abundance by construction, associate strongly with cell differentiation states. This association is not to be expected if cell differentiation is, in effect, regulated by epigenetic changes in gene expression. Based on these results, I postulate in this paper a falsifiable theory of differentiated multicellularity. This theory describes how the differentiated multicellular organism{\textemdash}understood as an intrinsic, higher-order, self-sufficient, self-repairing, self-replicating, and self-regulating dynamical constraint{\textemdash}emerges from proliferating undifferentiated cells. If it survives falsification tests consistently this theory would explain in principle (i) the self-regulated gene transcriptional changes during ontogeny and (ii) the emergence of differentiated multicellular lineages throughout evolution.}, URL = {https://www.biorxiv.org/content/early/2015/04/03/016840}, eprint = {https://www.biorxiv.org/content/early/2015/04/03/016840.full.pdf}, journal = {bioRxiv} }