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

Martin Arostegui, R. Wilder Scott, Kerstin Böse and T. Michael Underhill ()
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Martin Arostegui: University of British Columbia
R. Wilder Scott: University of British Columbia
Kerstin Böse: University of British Columbia
T. Michael Underhill: University of British Columbia

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32695-1

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