The cellular landscape of the endochondral bone during the transition to extrauterine life

Abstract

The cellular complexity of the endochondral bone underlies its essential and pleiotropic roles during organismal life. While the adult bone has received significant attention, we still lack a deep understanding of the perinatal bone cellulome. Here, we have profiled the full composition of the murine endochondral bone at the single-cell level during the transition from fetal to newborn life and in comparison with the adult tissue, with particular emphasis on the mesenchymal compartment. The perinatal bone contains different fibroblastic clusters with blastema-like characteristics in organizing and supporting skeletogenesis, angiogenesis and hematopoiesis. Our data also suggest dynamic inter- and intra-compartment interactions, as well as a bone marrow milieu that seems prone to anti-inflammation, which we hypothesize is necessary to ensure the proper program of lymphopoiesis and the establishment of central and peripheral tolerance in early life. Our study provides an integrative roadmap for the future design of genetic and cellular functional assays to validate cellular interactions and lineage relationships within the perinatal bone.

This work was supported by the Junta de Andalucía (PY20-00421 to JL-R) and the Spanish Ministerio de Ciencia e Innovación (María de Maeztu Institutional Grant CEX2020-001088-M to JL-R and JJT). We thank the rest of the members of the groups for scientific discussions and technical help. We are also grateful to A Franco, C Mateos, A López, P López and L Pérez for excellent mouse husbandry as well as the rest of the CABD Core services, in particular C Díaz (Flow Cytometry Facility). This manuscript was peer reviewed as a preprint by Review Commons prior to transfer to Immunology & Cell Biology.