A molecularly defined subpopulation of oligodendrocyte precursor cells controls the generation of myelinating oligodendrocytes during postnatal development.

Oligodendrocyte precursor cells (OPCs) are a class of glial cells that uniformly tiles the entire central nervous system (CNS). They play several key functions across the brain including the generation of oligodendrocytes and the control of myelination. Whether the functional diversity of OPCs is the result of genetically defined subpopulations or of their regulation by external factors has not been definitely established. We discovered that a subpopulation of OPCs found across the brain is defined by the expression of C1ql1, a gene previously described for its synaptic function in neurons. This subpopulation starts to appear during the first postnatal week in the mouse cortex. Ablation of C1ql1-expressing OPCs in the mouse leads to a massive lack of oligodendrocytes and myelination in many brain regions. This deficit cannot be rescued, even though some OPCs escape Sox10-driven ablation and end up partially compensating the OPC loss in the adult. Therefore, C1ql1 is a molecular marker of a functionally non-redundant subpopulation of OPCs, which controls the generation of myelinating oligodendrocytes.

Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development.

Connective tissue (CT), which includes tendon and muscle CT, plays critical roles in development, in particular as positional cue provider. Nonetheless, our understanding of fibroblast developmental programs is hampered because fibroblasts are highly heterogeneous and poorly characterized. Combining single-cell RNA-sequencing-based strategies including trajectory inference and in situ hybridization analyses, we address the diversity of fibroblasts and their developmental trajectories during chicken limb fetal development. We show that fibroblasts switch from a positional information to a lineage diversification program at the fetal period onset. Muscle CT and tendon are composed of several fibroblast populations that emerge asynchronously. Once the final muscle pattern is set, transcriptionally close populations are found in neighboring locations in limbs, prefiguring the adult fibroblast layers. We propose that the limb CT is organized in a continuum of promiscuous fibroblast identities, allowing for the robust and efficient connection of muscle to bone and skin.