Scientists Reveal Genetic Roadmap to Building an Entire Organism

 


All multicellular life, including humans, worms, and blue whales, begins as a single-celled egg. 


Each new cell that develops in the right place at the right time to carry out a specific function in coordination with its neighbors emerges from this one single cell, creating the galaxy of other cells necessary to construct an organism. 


Despite decades of research, biologists have not been able to fully comprehend this feat, which is one of the most remarkable in nature. 



Researchers from Harvard Medical School and Harvard University now describe in three landmark studies that were published in Science how they systematically profiled every cell in developing zebrafish and frog embryos to establish a path that reveals how a single cell builds an entire organism. 


The research teams followed the progress of individual cells over the first 24 hours of an embryo's life using single-cell sequencing technology. As embryonic cells transition into new states and types, their analyses reveal the comprehensive landscape of which genes are turned on or off and at what times


A list of genetic "recipes" for creating cell types in two important model species is provided by three studies from Harvard, the Massachusetts Institute of Technology, and Harvard Medical School. According to the researchers, the work may lead to a new understanding of numerous diseases. It is an unprecedented resource for studying disease and developmental biology


One At A Time

A copy of the organism's entire genome is carried within each embryonic cell. For the embryo to develop properly, cells must express the necessary genes at the appropriate time. Two well-studied model species, western claw-toed frog embryos, were the subjects of research


The teams' findings mirrored much of what was previously known about embryonic development in both species, demonstrating the effectiveness of the new methods. However, the analyses revealed the cascades of events that move cells from their early progenitor or "generalist" states to more specialized states with narrowly defined functions in unprecedented detail. 


The teams linked new, highly specific gene-expression patterns to various cell lineages and identified otherwise difficult-to-detect details like rare cell types and subtypes. In a few instances, they discovered cell types forming much earlier than previously thought. 


These data could be very helpful to researchers trying to find answers to questions about human disease. In regenerative medicine, for example, researchers have worked for decades to change the fates of stem cells so that they can replace damaged cells, tissues, or organs with ones that work. Recently gathered insights concerning the succession of quality articulation changes that accelerate the development of explicit cell types can push these endeavors further. 


If someone wants to make a particular type of cell, they now have the recipe for the steps those cells took as they formed in the embryo thanks to these datasets, according to Klein. In a way, we have set an example for how to systematically reconstruct these kinds of processes and established a gold standard for how complex differentiation processes actually progress in embryos. 


According to Klein, single-cell sequencing can provide previously unattainable insights when utilized in conjunction with one of the fundamental ideas of biological inquiry, which is the idea of disrupting a system to observe what happens. 


Using the CRISPR/Cas9 gene editing system, Klein, and their colleagues created mutant chord I-N expressing zebrafish as a proof of concept. Chord I-N is a gene that controls an embryo's orientation from back to front. Schier and colleagues profiled zebrafish with the one-eyed pinhead mutation in a different patterning gene similarly

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