TY  - JOUR
A1  - Kleefeldt, Florian
A1  - Upcin, Berin
A1  - Bömmel, Heike
A1  - Schulz, Christian
A1  - Eckner, Georg
A1  - Allmanritter, Jan
A1  - Bauer, Jochen
A1  - Braunger, Barbara
A1  - Rueckschloss, Uwe
A1  - Ergün, Süleyman
T1  - Bone marrow-independent adventitial macrophage progenitor cells contribute to angiogenesis
JF  - Cell Death & Disease
N2  - Pathological angiogenesis promotes tumor growth, metastasis, and atherosclerotic plaque rupture. Macrophages are key players in these processes. However, whether these macrophages differentiate from bone marrow-derived monocytes or from local vascular wall-resident stem and progenitor cells (VW-SCs) is an unresolved issue of angiogenesis. To answer this question, we analyzed vascular sprouting and alterations in aortic cell populations in mouse aortic ring assays (ARA). ARA culture leads to the generation of large numbers of macrophages, especially within the aortic adventitia. Using immunohistochemical fate-mapping and genetic in vivo-labeling approaches we show that 60% of these macrophages differentiate from bone marrow-independent Ly6c\(^{+}\)/Sca-1\(^{+}\) adventitial progenitor cells. Analysis of the NCX\(^{−/-}\) mouse model that genetically lacks embryonic circulation and yolk sac perfusion indicates that at least some of those progenitor cells arise yolk sac-independent. Macrophages represent the main source of VEGF in ARA that vice versa promotes the generation of additional macrophages thereby creating a pro-angiogenetic feedforward loop. Additionally, macrophage-derived VEGF activates CD34\(^{+}\) progenitor cells within the adventitial vasculogenic zone to differentiate into CD31\(^{+}\) endothelial cells. Consequently, depletion of macrophages and VEGFR2 antagonism drastically reduce vascular sprouting activity in ARA. In summary, we show that angiogenic activation induces differentiation of macrophages from bone marrow-derived as well as from bone marrow-independent VW-SCs. The latter ones are at least partially yolk sac-independent, too. Those VW-SC-derived macrophages critically contribute to angiogenesis, making them an attractive target to interfere with pathological angiogenesis in cancer and atherosclerosis as well as with regenerative angiogenesis in ischemic cardiovascular disorders.
KW  - macrophages
KW  - angiogenesis
KW  - bone marrow-derived monocytes
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299724
VL  - 13
IS  - 3
ER  - 
TY  - JOUR
A1  - Koeniger, Tobias
A1  - Bell, Luisa
A1  - Mifka, Anika
A1  - Enders, Michael
A1  - Hautmann, Valentin
A1  - Mekala, Subba Rao
A1  - Kirchner, Philipp
A1  - Ekici, Arif B.
A1  - Schulz, Christian
A1  - Wörsdörfer, Philipp
A1  - Mencl, Stine
A1  - Kleinschnitz, Christoph
A1  - Ergün, Süleyman
A1  - Kuerten, Stefanie
T1  - Bone marrow‐derived myeloid progenitors in the leptomeninges of adult mice
JF  - Stem Cells
N2  - 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. Flt3\(^{Cre}\) 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.
KW  - hematopoietic
KW  - meninges
KW  - mouse
KW  - myeloid
KW  - progenitor
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224452
VL  - 39
IS  - 2
SP  - 227
EP  - 239
ER  -