Scientists at the Francis Crick Institute have created human stem cell models that include notochord for the first time. The notochord is a vital tissue in an embryo that helps direct cells to form the spine and nervous system.
Researchers at the Francis Crick Institute have produced human stem cell models1 that uniquely feature notochord—a critical tissue in developing embryos which guides cells in constructing the spine and trunk nervous system.
This research, published today in Nature, represents a major advancement in our understanding of human body formation during early development.
The notochord is a rod-like structure essential for creating the body’s framework. It’s a key characteristic of all vertebrates and plays a vital role in organizing the developing embryonic tissues.
Even though the notochord is crucial, its intricate structure has been absent in previous lab-generated models of human trunk development.
In this study, the scientists began by examining chicken embryos to observe the natural formation of the notochord. By correlating their findings with previously published data from mouse and monkey embryos, they determined the precise timing and series of molecular signals necessary for generating notochord tissue.
Using this information, they devised an exact series of chemical signals to stimulate human stem cells into producing a notochord.
The stem cells developed a miniature ‘trunk-like’ structure that grew spontaneously to lengths of 1-2 millimeters. This structure contained developing neural tissue and bone stem cells, organized in a manner that closely resembles human embryonic development. This indicates that the notochord effectively guides cells to differentiate into the correct tissue type in the appropriate location and time.
The researchers believe this study could aid in understanding birth defects related to the spine and spinal cord. It could also shed light on issues concerning intervertebral discs—those shock-absorbing pads that emerge from the notochord, which often lead to back pain as they degenerate with aging.
James Briscoe, the Group Leader of the Developmental Dynamics Laboratory and the study’s senior author, remarked, “The notochord serves as a GPS for the developing embryo, establishing the body’s primary axis and directing spine and nervous system formation. Generating this essential tissue in the lab has been challenging, hindering our research on human development and related disorders. Now that we’ve successfully created a working model, we can explore developmental conditions that have previously been poorly understood.”
Tiago Rito, Postdoctoral Fellow in the Developmental Dynamics Laboratory and the study’s lead author, stated, “Identifying the exact chemical signals for notochord production was akin to discovering the right recipe. Earlier attempts to cultivate notochord in the lab likely fell short due to a lack of understanding regarding the timing for adding the necessary components.”
“What’s particularly thrilling is that the notochord within our lab-grown structures seems to operate similarly to its role in a developing embryo. It emits chemical signals that help organize surrounding tissues, just like it would during normal development.”
