Complex animals, such as mice and humans are basically three layered organisms: We have inside (endoderm), middle (mesoderm) and outside (ectoderm) layers. These three layers form very early in embryonic development, and will form different tissues that make up the complete organism. For example, the endoderm will go on to form the internal organs, such as the liver and the intestines. The mesoderm forms the middle tissues, such as the heart and the muscles, whilst the ectoderm forms the outer tissues such as the skin and brain.

These three layers have traditionally been defined by careful morphological and anatomical observation and experiment. In the work published by Andrew Hutchins and his team, they instead take a computational approach to redefine these layers. Using nearly 1000 RNA-seq gene expression samples, which cover 272 tissues, they build computational models of these three layers. These computational models can accurately recover the three known layers: endoderm, mesoderm, and the ectoderm, along with early embryonic cells. Intriguingly their models indicated the existence of other layers, the immune system (blood mesoderm), the jaw and facial structures (neural crest) and the skin (surface ectoderm).

Additionally, they discover the ‘master regulator’ genes that are controlling each layer, and which block cells from converting between domains. These models have implications for understanding trans-lineage differentiation for stem cells, developmental cell biology and regenerative medicine.  

This work was performed in collaboration with the Guangzhou Institutes of Biomedicine and Health (Chinese Academy of Science) and was published in the leading journal Nucleic Acids Research, titled: “Models of global gene expression define major domains of cell type and tissue identity”.

Web address：https://academic.oup.com/nar/article/doi/10.1093/nar/gkx054/2962564/Models-of-global-gene-expression-define-major

DOI: https://doi.org/10.1093/nar/gkx054