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Publication : A single-cell census of mouse limb development identifies complex spatiotemporal dynamics of skeleton formation.

First Author  Markman S Year  2023
Journal  Dev Cell Volume  58
Issue  7 Pages  565-581.e4
PubMed ID  36931270 Mgi Jnum  J:334725
Mgi Id  MGI:7463867 Doi  10.1016/j.devcel.2023.02.013
Citation  Markman S, et al. (2023) A single-cell census of mouse limb development identifies complex spatiotemporal dynamics of skeleton formation. Dev Cell 58(7):565-581.e4
abstractText  Limb development has long served as a model system for coordinated spatial patterning of progenitor cells. Here, we identify a population of naive limb progenitors and show that they differentiate progressively to form the skeleton in a complex, non-consecutive, three-dimensional pattern. Single-cell RNA sequencing of the developing mouse forelimb identified three progenitor states: naive, proximal, and autopodial, as well as Msx1 as a marker for the naive progenitors. In vivo lineage tracing confirmed this role and localized the naive progenitors to the outer margin of the limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that the progressive transition of Msx1(+) naive 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 an alternative model for limb skeleton development.
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