Bone marrow-derived myeloid progenitors in the leptomeninges of adult mice

Abstract

Although the bone marrow contains most hematopoietic activity during adulthood, hematopoietic stem and progenitor cells can be recovered from various extramedullary sites. Cells with hematopoietic progenitor properties have even been reported in the adult brain under steady-state conditions, but their nature and localization remain insufficiently defined. Here, we describe a heterogeneous population of myeloid progenitors in the leptomeninges of adult C57BL/6 mice. This cell pool included common myeloid, granulocyte/macrophage, and megakaryocyte/erythrocyte progenitors. Accordingly, it gave rise to all major myelo-erythroid lineages in clonogenic culture assays. Brain-associated progenitors persisted after tissue perfusion and were partially inaccessible to intravenous antibodies, suggesting their localization behind continuous blood vessel endothelium such as the blood-arachnoid barrier. Flt3Cre lineage tracing and bone marrow transplantation showed that the precursors were derived from adult hematopoietic stem cells and were most likely continuously replaced via cell trafficking. Importantly, their occurrence was tied to the immunologic state of the central nervous system (CNS) and was diminished in the context of neuroinflammation and ischemic stroke. Our findings confirm the presence of myeloid progenitors at the meningeal border of the brain and lay the foundation to unravel their possible functions in CNS surveillance and local immune cell production.

Skull and vertebral bone marrow in central nervous system inflammation

“…Notably, administration of the US Food and Drug Administration approved β3-adrenergic receptor agonist mirabegron stimulates the production of immunomodulatory monocytes in the bone marrow, reducing neuroinflammation and improving ICH outcomes. Furthermore, a recent report demonstrated that a heterogeneous population of myeloid progenitors in the leptomeninges appeared to be continuously recruited from elsewhere, supporting the theory that bone marrow-derived immune cell mobilization is involved in active CNS immune surveillance and neuroinflammation [42] .…”

Inhibition of Notch Signaling Stimulates Osteoclastogenesis From the Common Trilineage Progenitor Under Inflammatory Conditions

“…The mononuclear phagocyte system is a family of cells including progenitors, circulating blood monocytes, resident tissue macrophages and dendritic cells as well as bone-associated osteoclasts ( 12 , 48 ). Even during adulthood, myeloid progenitors of hematopoietic origin retain a certain degree of plasticity and mobility, and can be recovered from medullary and extramedullary sites, such as the spleen, liver, muscle, lungs and intestine ( 49 ). We showed that in the adult mouse bone marrow, the common trilineage progenitor can be defined as the CD45 + Ly6G − CD3 − B220 − NK1.1 − CD11b –/lo CD115 + subset, comprising around 5% of total hematopoietic cells.…”

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

“…Another Anti-CD45-SAP publication showed potential for treatment for RAG (Recombination activating genes) deficiency–an autosomal recessive disease that produces immunodeficiency [ 42 ]. Bone marrow chimeric mice generated using Anti-CD45-SAP have been utilized to confirm the presence of myeloid progenitors at the meningeal border of the brain, and to lay a foundation to unravel possible functions in central nervous system (CNS) surveillance and local immune cell production [ 91 ].…”