First spatial map of human limb development reveals unexpected insights


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Human fingers and toes do not grow outward; Instead, they develop from a large basal bud, with the intervening cells retracting to reveal the digits below. This is one of many processes captured for the first time, as scientists publish a spatial cell atlas of the entire developing human limb, resolved in space and time.

The Wellcome Sanger Institute, Sun Yat-sen University, EMBL’s European Bioinformatics Institute and collaborators used state-of-the-art single-cell and spatial techniques to create an atlas representing the cellular topography of early human joints, pinpointing the exact location of cells.

The study is part of the International Human Cell Atlas initiative to map every cell type in the human body, changing the understanding of health and disease.

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Atlas, released today (December 6). NatureProvides an openly available resource that captures the complex processes that govern the rapid growth of joints during the early stages of joint formation2.

Atlas reveals new links between growth cells and some congenital joint syndromes such as short fingers and extra digits.

Limbs appear initially as undifferentiated sacs of cells on the sides of the body, without a specific shape or function. However after 8 weeks of development, they are well differentiated, anatomically complex and readily recognizable as limbs, complete with fingers and toes. This requires very rapid and precise orchestration of cells. Any small disturbance in this process can have a downstream effect, which is why limb anomalies are one of the most frequently reported syndromes at birth, affecting one in 500 births worldwide3.

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Although limb development has been studied extensively in rat and chick models, it is unclear to what extent they reflect the human situation. However, advances in technology are now enabling researchers to explore the early stages of human limb formation.

In this new study, scientists from the Wellcome Sanger Institute, Sun Yat-sen University and their collaborators examined tissues between 5 and 9 weeks of development. This allowed us to identify specific gene expression programs, activated at certain times and in specific regions, that shape the developing limbs.

Special staining of the tissue clearly revealed how cell populations differed in the patterns of digits they formed.

As part of the study, the researchers demonstrated that certain genetic patterns in how hands and feet develop, identifying certain genes that, when disrupted, are associated with specific limb syndromes such as brachydactyly – short fingers – and polysyndactyly – extra fingers or toes.

The team was also able to confirm that many aspects of joint development are shared between humans and mice.

Collectively, these findings not only provide in-depth characterization of joint development in humans, but also provide important insights that may impact the diagnosis and treatment of congenital joint syndromes.

Professor Hongbo Zhang, senior author of the study at Sun Yat-sen University, Guangzhou, said: „Decades of studying model organisms established the basis for our understanding of vertebrate limb development. However, characterizing this in humans has been elusive until now, and we have not been able to infer the relevance of mouse models to human development. What we reveal is It’s a very complex and precisely regulated process. It’s like watching a sculptor at work, chipping away at a block of marble to reveal a masterpiece. In this case, nature is the sculptor, resulting in the incredible complexity of our fingers and toes.

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Dr. Sarah Teichmann, senior author of the study at the Wellcome Sanger Institute and co-founder of the Human Cell Atlas, said: „For the first time, we have been able to capture the remarkable process of limb development down to single-cell resolution. In space and time. Our work in the Human Cell Atlas provides insight into how anatomically complex structures form. Deepening our understanding, enabling us to discover the genetic and cellular processes behind healthy human development, there are many implications for research and health care.For example, we discovered new roles for key genes. M.Sc And PITX1 It regulates muscle stem cells. This may offer the possibility of treating muscle-related disorders or injuries.”

Note: Zhang P, He P, Lawrence JEG, et al. A human embryonic limb cell atlas resolved in space and time. Nature. 2023. doi: 10.1038/s41586-023-06806-x

This article has been reprinted from the following materials. Note: Material may have been edited for length and content. For more information, please contact the source cited.

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