For the first, scientists have generated human stem cell models containing notochord – a tissue in the developing embryo. Notochord acts like the body’s navigation system, directing cells where to build the spine and the nervous system.
Researchers at the Francis Crick Institute conducted the study to investigate how human pluripotent stem cells develop trunk (the nervous system) cell types. This progression could be a significant leap in studying how the human body shapes during early development.
The notochord is a rod-shaped tissue that plays a vital role in the scaffold of the developing body. It is a defining feature of all animals with a backbone and is critical in organizing tissues in the developing embryo.
The formation of the vertebrate body involves the coordinated production of trunk tissues. Though in vitro models use pluripotent stem cells to replicate aspects of this process, they often lack notochord.
“The notochord acts like a GPS for the developing embryo, helping to establish the body’s main axis and guiding the formation of the spine and nervous system,” says James Briscoe, the senior author of the study.
“Until now, it’s been difficult to generate this vital tissue in the lab, limiting our ability to study human development and disorders. Now that we’ve created a model which works, this opens doors to study developmental conditions which we’ve been in the dark about,” James continues.
In a study published in Nature, researchers counted on studying chicken embryos to glimpse how the notochord forms naturally. By integrating the data from this observation with the information on monkey and mouse embryos, researchers were able to establish the line of succession of the molecular signals needed to create notochord tissue.
Using this timing and sequence, scientists derived a precise sequence of chemical signals that stimulate human stem cells to form a notochord.
As per their observation, the stem cells formed a trunk-like structure of 1-2 millimeters in length. This structure included developing neural tissue and bone stem cells, whose arrangement closely resembles the development in human embryos. Experimenters indicated that the notochord encourages cells to become the right type of tissue at the right place and time.
Scientists Create Artificial Embryo Structure Using Stem Cells
This advancement in the notochord formation could help to study birth defects affecting the spine and spinal cord. Researchers believe it could also provide insights into the conditions affecting the intervertebral discs with the progressing age.
The lead author Tiago Rito says, “Finding the exact chemical signals to produce notochord was like finding the right recipe. Previous attempts to grow the notochord in the lab may have failed because we didn’t understand the required timing to add the ingredients.“
“What’s particularly exciting is that the notochord in our lab-grown structures appears to function similarly to how it would in a developing embryo. It sends out chemical signals that help organize surrounding tissue, just as it would during typical development.“
Journal Reference
- Rito, T., Libby, A. R., Demuth, M., Domart, M., & Briscoe, J. (2024). Timely TGFβ signalling inhibition induces notochord. Nature 1-10 (2024). DOI: 10.1038/s41586-024-08332-w
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