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Developmental biology - Cellular Identity|
Who am I? How cells find their identity
"The RNA tells us, which genes are active and determines the function and characteristics of a cell."
In order to merge and compare the data, Schier's team developed a new software (URD). While previous studies in this field are based on the examination of a handful of genes, the new high-throughput single-cell RNA sequencing method enables the analysis of all active genes during cell development. With this new technology, the team has been able to reconstruct, for the first time, a widely branched tree that traces the development of each individual cell, starting with the fertilized egg cell. In addition, they mapped the cells to their spatial origin in the early embryo.
Finding cell identity is more flexible than expected
The results show that the genetic program that a cell follows on the way to maturity is by no means set in stone.
"It seems that the developmental path of a cell is more flexible than we previously expected."
So far, it was assumed that developing cells follow a predetermined path, like marbles rolling down a hill until they stop at their predestined place. The study now suggests that signals from the environment can have such a strong influence on the cells, that they leave the initial trajectory and change their path, thus taking on a new identity.
Entire development as a cell lineage tree
In a next step, the research group will expand the cell lineage tree, investigate more cell types and follow the development of cells over a longer period of time.
"My aim is to merge the developmental trajectories and the lineage trees to one complete whole. If we can understand the logic behind cell differentiation, we may, one day, be able to answer the question: How many ways are there to build a heart or a brain?"
During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these transcriptional trajectories during zebrafish embryogenesis, we sequenced 38,731 cells and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the trajectories of 25 cell types through early somitogenesis, gene expression along them, and their spatial origin in the blastula. Analysis of Nodal signaling mutants revealed that their transcriptomes were canalized into a subset of wild-type transcriptional trajectories. Some wild-type developmental branchpoints contained cells expressing genes characteristic of multiple fates. These cells appeared to trans-specify from one fate to another. These findings reconstruct the transcriptional trajectories of a vertebrate embryo, highlight the concurrent canalization and plasticity of embryonic specification, and provide a framework to reconstruct complex developmental trees from single-cell transcriptomes.
Authors: Jeffrey A. Farrell1, Yiqun Wang1, Samantha J. Riensenfeld, Karthik Shekhar, Aviv Regev, Alexander F. Schier
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During embryogenesis, cells acquire distinct fates. To uncover what these are, researchers sequenced 38,731 cells and developed a computational reconstruction method, URD, to identify cell trajectories of 25 types through to the early blastula stage. Analysis reflected cells with genes characteristic of multiple fates with cells that appear to jump from one fate to another. These findings highlight the plasticity of embryonic specification, providing a framework to reconstruct complex developmental trees. Image credit: Darryl Leja.