학술논문

Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult
Document Type
Original Paper
Source
Nature Communications. 13(1)
Subject
Language
English
ISSN
2041-1723
Abstract
Tissue development and regeneration rely on the cooperation of multiple mesenchymal progenitor (MP) subpopulations. We recently identified Hic1 as a marker of quiescent MPs in multiple adult tissues. Here, we describe the embryonic origin of appendicular Hic1+ MPs and demonstrate that they arise in the hypaxial somite, and migrate into the developing limb at embryonic day 11.5, well after limb bud initiation. Time-resolved single-cell-omics analyses coupled with lineage tracing reveal that Hic1+ cells generate a unique MP hierarchy, that includes both recently identified adult universal fibroblast populations (Dpt+, Pi16+ and Dpt+Col15a1+) and more specialised mesenchymal derivatives such as, peri and endoneurial cells, pericytes, bone marrow stromal cells, myotenocytes, tenocytes, fascia-resident fibroblasts, with limited contributions to chondrocytes and osteocytes within the skeletal elements. MPs endure within these compartments, continue to express Hic1 and represent a critical reservoir to support post-natal growth and regeneration.
Mesenchymal progenitors (MPs) are fundamental to tissue development and regeneration, however, their embryonic origin is unclear. Single cell-omics coupled with lineage tracing reveal a unique somite-derived MP hierarchy in limb morphogenesis.