Human Body Plan Emergence from iPSCs and Somites Study
Author: Kyoto University
Published: 2022/12/25 - Updated: 2026/01/19
Publication Details: Peer-Reviewed, Research, Study, Analysis
Category Topic: Organoids - Related Publications
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research presents a peer-reviewed study that reconstructs key early stages of the human body plan using induced pluripotent stem cells (iPSCs) to generate somite-like structures in a three-dimensional culture, capturing both molecular and morphological traits of embryonic development. The findings are authoritative because they are published in a respected scientific journal and apply rigorous experimental design to recapitulate human somitogenesis outside the embryo, offering a scalable platform to investigate how the vertebral column, muscles, and related tissues form and how genetic mutations contribute to spine and musculoskeletal disorders. Such insight is useful for scientists, clinicians, and individuals affected by congenital spinal conditions, including some disabilities and age-related skeletal issues, because it enhances understanding of developmental mechanisms that underlie structural anomalies - Disabled World (DW).
- Definition: Somites
Somites are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide into the dermatomes, myotomes, sclerotomes and syndetomes that give rise to the vertebrae of the vertebral column, rib cage, part of the occipital bone, skeletal muscle, cartilage, tendons, and skin of the back. Different species have different numbers of somites. For example, frogs have approximately 10, humans have 37, chicks have 50, mice have 65, and snakes have more than 300, up to about 500. Somite number is unaffected by changes in the size of the embryo through experimental procedure. Because all developing embryos of a particular species form the same number of somites, the number of somites present is typically used as a reference for age in developing vertebrates.
Introduction
Reconstituting Human Somitogenesis In Vitro.
Although Michelangelo's masterpiece David captured the magnificence of the human body - how this exquisite body plan was established during human development has puzzled scientists for more than a century. A new study led by ASHBi researchers, published in Nature, uncovers using their own mallet and chisel - a petri dish and induced pluripotent stem cells (iPSCs) - how the early stages of the human body plan are established.
Main Content
However, now, work published in Nature by an international team of scientists led by Dr. Cantas Alev at the Institute for the Advanced Study of Human Biology (ASHBi) in Kyoto University has uncovered using their own mallet and chisel - a petri dish and induced pluripotent stem cells (iPSCs) - how the early stages of the human body plan are established.
Similar to other organisms within the animal kingdom, the human body consists of repetitive anatomical units or segments - a prominent example being the vertebrae of the human spine. The most primitive version of such segments in the human embryo, known as somites, arise from an embryonic tissue called presomitic mesoderm (PSM) and contribute to the formation of various structures, including cartilage, bone, skin, and skeletal muscle.
While previous work by Alev and colleagues reconstituted the so-called segmentation clock, a molecular oscillator and dynamic 'wave' of gene expression required for the proper formation of human somites (somitogenesis), it could not recapitulate the complex three-dimensional (3-D) morphological and structural changes occurring during human body-axis development.
In their new study, Alev and co-workers, using a cocktail consisting of human iPSCs-derived cells and Matrigel - a viscous gel compound enriched with extracellular matrix components - has now generated a 3-D model that can recapitulate the development of our early body plan in a dish, which they coined 'axioloids.'
"(Our) axioloids capture not only the oscillatory nature of the segmentation clock but also the molecular as well as the 3-D morphological and structural characteristics observed during the process of segmentation and somitogenesis," says Alev.
By taking a bottom-up approach in their experimental design, Alev and his team identified a previously unappreciated functional role for retinoids, more commonly known as vitamin A and its derivatives, during somite formation.
"Our bottom-up approach was critical to unraveling the role of retinoids during somitogenesis. Many researchers likely missed this essential role because vitamin A is a common supplement that usually gets included in culture media," comments Alev.
When Alev's axioloids were compared to actual human embryos, they revealed "remarkable similarities to Carnegie Stage 9-12 human embryos, which is known to be a critical stage during human development where organs such as the brain and heart start forming" explains Alev.
Lastly, using iPSCs containing mutations commonly associated with congenital spine disease, Alev and co-authors demonstrated that axioloids could be instrumental in delineating how these mutations contribute to the pathogenesis of such diseases.
Alev Comments:
"Our (bottom-up) approach of generating axioloids has not only allowed us to uncouple fundamental biological processes, such as cell morphology and cell states, but it allowed us to determine how mutations contribute to spine disease" and he continues, "we also anticipate similar strategies will become increasingly necessary to understand better the etiology and pathology of other diseases."
These findings, together with another complementary study from researchers at Harvard Medical School, were published in Nature on December 21, 2022.
Insights, Analysis, and Developments
Editorial Note: By successfully modeling human somite formation in vitro with iPSCs, this work not only advances fundamental embryology but also lays a practical foundation for dissecting the origins of vertebral and musculoskeletal disorders. Its implications extend to more precise disease modeling and potentially to future regenerative strategies that address conditions impacting mobility and quality of life - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Kyoto University and published on 2022/12/25, this content may have been edited for style, clarity, or brevity.