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Single-cell atlas of mouse limb development reveals a complex spatiotemporal dynamics of skeleton formation

View ORCID ProfileSvetlana Markman, Mor Zada, Eyal David, Amir Giladi, Ido Amit, Elazar Zelzer
doi: https://doi.org/10.1101/2022.05.07.490557
Svetlana Markman
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
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Mor Zada
2Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
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Eyal David
2Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
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Amir Giladi
2Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
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Ido Amit
2Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
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Elazar Zelzer
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
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  • For correspondence: eli.zelzer@weizmann.ac.il
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Abstract

Limb development has long served as a model system for coordinated spatial patterning of progenitor cells. Here, we identify a population of naïve limb progenitors and show that they differentiate progressively to form the skeleton in a complex nonconsecutive three-dimensional pattern.

Single-cell RNA sequencing of the developing mouse forelimb revealed three progenitor states: naïve, proximal and autopodial, as well as Msx1 as a marker for the naïve progenitors. In vivo lineage tracing confirmed this role and localized the naïve progenitors to the outer margin of the limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that the progressive transition of Msx1+ naïve progenitors into proximal and autopodial progenitors coincides with their differentiation to Sox9+ chondroprogenitors, which occurs along all the forming skeletal segments.

Indeed, tracking the spatiotemporal sequence of differentiation showed that the skeleton forms progressively in a complex pattern. These findings suggest a new model for limb skeleton development.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185940

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 07, 2022.
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Single-cell atlas of mouse limb development reveals a complex spatiotemporal dynamics of skeleton formation
Svetlana Markman, Mor Zada, Eyal David, Amir Giladi, Ido Amit, Elazar Zelzer
bioRxiv 2022.05.07.490557; doi: https://doi.org/10.1101/2022.05.07.490557
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Single-cell atlas of mouse limb development reveals a complex spatiotemporal dynamics of skeleton formation
Svetlana Markman, Mor Zada, Eyal David, Amir Giladi, Ido Amit, Elazar Zelzer
bioRxiv 2022.05.07.490557; doi: https://doi.org/10.1101/2022.05.07.490557

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