Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult

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...

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Bibliographic Details
Published in:Nature communications 2022-08, Vol.13 (1), p.4989-4989, Article 4989
Main Authors: Arostegui, Martin, Scott, R. Wilder, Böse, Kerstin, Underhill, T. Michael
Format: Article
Language:English
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Bone marrow
Cell cycle
Chondrocytes
Embryogenesis
Embryos
Fascia
Fibroblasts
Genes
Humanities and Social Sciences
Limb buds
Mesenchyme
Morphogenesis
multidisciplinary
Musculoskeletal system
Osteocytes
Pericytes
Population
Progenitor cells
Regeneration
Science
Science (multidisciplinary)
Stromal cells
Subpopulations
Taxonomy
Tissues
Tracing
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Summary: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.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-32695-1