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Publications of the Week

Paraxial Mesoderm Organoids Model Development of Human Somites

By February 14, 2022March 14th, 2022No Comments

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This week we profile a recent publication in eLife from the lab of Dr. Sahand Hormoz at Dana-Farber Cancer Institute.

Can you provide a brief overview of your lab’s current research focus?

Cells occupy distinct phenotypic and molecular states during development and in diseases. Our lab works on deciphering the dynamics of transitions between these states with the hope of ultimately controlling them for biomedical applications. For example, we are trying to understand how mutated blood stem cells proliferate and differentiate in patients with blood cancers. We are also trying to differentiate stem cells into useful cell types for regenerative medicine. We develop new technologies to characterize molecular states of single cells and in many occasions we also develop new mathematical frameworks to analyze the data that our experiments generate.

What is the significance of the findings in this publication?

During embryo development, humans and other animals with backbones (called vertebrates) repeatedly grow pairs of segments along the major body axis that runs from the head to the tail of the embryo. These segments, called somites, will later give rise to parts of the skeleton, as well as the associated muscle, cartilage, tendons, and skin. Most of what we know about how these segments form during animal development comes from studies in chicken, zebrafish, and mice. However, to date, we know very little about how the process of segment formation happens in humans since there is no experimental way we can directly observe this process. We also don’t know how similar segment formation is compared to other vertebrate animals that we were able to study in more detail. This process is important to understand because when it goes wrong, it can lead to an abnormal curvature in the spine at birth, which affects about 1 in 10,000 newborns.

To recapitulate human segment formation in a dish, we used human pluripotent stem cells, which are capable of making any cell type in the body. To mimic the process that normally occurs in the embryo, we first let a defined number of stem cells form a cluster of cells (aggregate). Then we guided the stem cells to differentiate into cell types that make up somites in the embryo. This differentiation process is highly regulated and typically happens without problems in the embryo. However, the process in a dish is much less well controlled. We systematically tested many conditions to figure out a way to reproducibly make 3D tissue structures (called organoids) that form somites from human stem cells. We also confirmed that the organization and size of somites, as well as the genes they turn on and off, are very similar to what we know about vertebrate somites.

Somitoid striking image

Somitoids are human paraxial mesoderm organoids derived from hPSCs, which recapitulate the molecular, morphological and functional features of paraxial mesoderm development, including formation of somite-like structures in vitro.

What are the next steps for this research?

This new model of human segment formation is the first model of its kind which now allows us and other researchers to better understand how segments form in humans. It might also allow researchers to investigate what exactly goes wrong when vertebrae fail to form completely or when they fuse together causing a sideways curvature in newborns.

If you’d like to mention your funding sources, please list them.

This research in our paper was funded by NIH National Heart, Lung, and Blood Institute (R01HL158269), National Institutes of Health (P01GM099117), and Chan Zuckerberg Initiative (2018-183143).

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