PT  - JOURNAL ARTICLE
AU  - Markman, Svetlana
AU  - Zada, Mor
AU  - David, Eyal
AU  - Giladi, Amir
AU  - Amit, Ido
AU  - Zelzer, Elazar
TI  - Single-cell atlas of mouse limb development reveals a complex spatiotemporal dynamics of skeleton formation
AID  - 10.1101/2022.05.07.490557
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.07.490557
4099  - http://biorxiv.org/content/early/2022/05/07/2022.05.07.490557.short
4100  - http://biorxiv.org/content/early/2022/05/07/2022.05.07.490557.full
AB  - 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 StatementThe authors have declared no competing interest.