New insight into the cells that form spinal cord, muscle and bone tissue in mammalian embryos comes from a study by scientists at the Francis Crick Institute, the Max-Delbrück Center for Molecular Medicine, Berlin and the University of Edinburgh.
The discovery paves the way for generating these tissues from stem cells in the laboratory and could lead to new ways of studying degenerative conditions such as motor neuron disease and muscular dystrophy.
In embryos, the spinal cord, muscle and skeleton are produced from a group of cells called neuro-mesodermal progenitors (NMPs). These cells are few in number and exist only for a short time in embryos, despite giving rise to many tissues in the body. Their scarcity and inaccessibility has made studying NMPs challenging.
Now, by using the latest molecular techniques, the research team has for the first time deciphered gene activity in neuromesodermal progenitors. They used an advanced RNA sequencing technique called single-cell transcriptional profiling, which analyses individual cells to provide a detailed picture of gene activity in every cell.
Single-cell Transcriptional Profiling
The technique allowed the team to establish a molecular signature of NMPs and to show that NMPs produced from stem cells in petri dishes in the laboratory closely resemble those found in embryos. This enabled the team to use lab-grown NMPs to learn more about these cells and how they make spinal cord, muscle and bone tissue.
By manipulating the cells in petri dishes and testing the function of specific genes, the researchers re-constructed the regulatory mechanism and formulated a mathematical model that explains how neuromesodermal progenitors produce the appropriate amounts of spinal cord and musculoskeletal cells.
Dr James Briscoe, who led the research from the Francis Crick Institute said:
“For embryonic development to progress smoothly, NMPs must make the right types of cells, in the right numbers at the right time. Understanding how cells such as NMPs make decisions is therefore central to understanding embryonic development. Single cell profiling techniques, including the ones we used in this study, are giving us unprecedented insight into this problem and offering a new and fascinating view of how embryos produce the different tissues that make up adults."
The research was supported by the Francis Crick Institute, Cancer Research UK, the UK Medical Research Council, the Wellcome Trust and by the BBSRC.
Mina Gouti et al. A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development Developmental Cell (2017). DOI: 10.1016/j.devcel.2017.04.002
Image: Neurons (red) and muscle cells (green) produced from NMPs in the laboratory. Credit: James Briscoe, Francis Crick Institute