title: The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.
abstract: Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin(-) MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin(+) cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP(+) Pdgfrα(-) cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Isern
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: García-García
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Martín
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Arranz
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martín-Pérez
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Torroja
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Sánchez-Cabo
authors.affiliation: Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Simón
authors.identifier: http://orcid.org/0000-0002-9805-9988
authors.initials: S
authors.lastname: Méndez-Ferrer
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D020219:Chondrogenesis; D005333:Fetus / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D064231:Nestin / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology*; D025341:Principal Component Analysis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: D054377:Chemokine CXCL12; D064231:Nestin; D049452:Green Fluorescent Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: bone marrow; developmental biology; hematopoietic stem cells; mesenchymal stem cells; mouse; neural crest; stem cell niche; stem cells