scholarly journals Tie2+Bone Marrow Endothelial Cells Regulate Hematopoietic Stem Cell Regeneration Following Radiation Injury

Stem Cells ◽  
2013 ◽  
Vol 31 (2) ◽  
pp. 327-337 ◽  
Author(s):  
Phuong L. Doan ◽  
J. Lauren Russell ◽  
Heather A. Himburg ◽  
Katherine Helms ◽  
Jeffrey R. Harris ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Radiation Injury ◽  
Cell Regeneration ◽  
Hematopoietic Stem

scholarly journals Interleukin-33 regulates hematopoietic stem cell regeneration after radiation injury

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ping Huang ◽  
Xiangyong Li ◽  
Ying Meng ◽  
Baohong Yuan ◽  
Tao Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Radiation Injury ◽  
Cell Regeneration ◽  
Hematopoietic Stem ◽  
Interleukin 33

scholarly journals β-Galactosylceramidase Deficiency Causes Bone Marrow Vascular Defects in an Animal Model of Krabbe Disease

2019 ◽  
Vol 21 (1) ◽  
pp. 251
Author(s):  
Mirella Belleri ◽  
Daniela Coltrini ◽  
Marco Righi ◽  
Cosetta Ravelli ◽  
Sara Taranto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Krabbe Disease ◽  
Microscopy Imaging ◽  
Hematopoietic Stem

Krabbe disease (KD) is an autosomal recessive sphingolipidosis caused by the deficiency of the lysosomal hydrolase β-galactosylceramidase (GALC). Oligodendroglia degeneration and demyelination of the nervous system lead to neurological dysfunctions which are usually lethal by two years of age. At present, the only clinical treatment with any proven efficacy is hematopoietic stem-cell transplantation, which is more effective when administered in the neonatal period to presymptomatic recipients. Bone marrow (BM) sinusoidal endothelial cells (SECs) play a pivotal role in stem cell engraftment and reconstitution of hematopoiesis. Previous observations had shown significant alterations of microvascular endothelial cells in the brain of KD patients and in Galc mutant twitcher mice, an authentic model of the disease. In the present study, we investigated the vascular component of the BM in the femurs of symptomatic homozygous twitcher mice at postnatal day P36. Histological, immunohistochemical, and two-photon microscopy imaging analyses revealed the presence of significant alterations of the diaphyseal BM vasculature, characterized by enlarged, discontinuous, and hemorrhagic SECs that express the endothelial marker vascular endothelial growth factor receptor-2 (VEGFR2) but lack platelet/endothelial cell adhesion molecule-1 (CD31) expression. In addition, computer-aided image analysis indicates that twitcher CD31−/VEGFR2+ SECs show a significant increase in lumen size and in the number and size of endothelial gaps compared to BM SECs of wild type littermates. These results suggest that morphofunctional defects in the BM vascular niche may contribute to the limited therapeutic efficacy of hematopoietic stem-cell transplantation in KD patients at symptomatic stages of the disease.

scholarly journals Granulopoiesis in the Control of Hematopoietic Stem Cell Self-Renewal and Niches

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. SCI-21-SCI-21
Author(s):  
Daniel Lucas-Alcaraz
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
B Cell Differentiation ◽  
Hematopoietic Stem ◽  
Vascular Niche ◽  
Reciprocal Transplants ◽  
Response To Stress

Abstract The bone marrow (BM) vasculature is a critical component of the hematopoietic stem cell (HSC) niche. While the mechanisms through which the vasculature regulates HSC are intensively studied little is known about how this vascular niche is regulated and its function in supporting other aspects of hematopoiesis. We have recently shown that, after myeloablation, BM neutrophils are both sufficient and necessary for the regeneration of the vascular niche. This crosstalk is dependent of TNFα secretion by the neutrophil and TNFR1/TNFR2 expression in the stroma (Bowers et al., 2018). We now demonstrate that the crosstalk between neutrophils and the vasculature is bidirectional and that bone marrow endothelial cells provide a niche for fast neutrophil production in response to stress. Emergency granulopoiesis (EG) is the process through which the hematopoietic system generates large neutrophil numbers-at the expense of lymphocyte production-in response to inflammation or infection. A key EG driver is IL1. This cytokine can induce a myeloid bias on HSC and this is thought to be the main mechanism for IL1-driven EG. While characterizing the BM response to IL1 treatment we noted a fourfold reduction in erythropoiesis. Since erythroid- and myeloid- lineage cells differentiate from a common myeloid progenitor downstream of the HSC these results indicated that IL1 acted on other cells during EG. Differentiation analyses showed that IL1 blocks B cell differentiation at the common lymphoid progenitor and Pro-B to Pre-B transition stages whereas loss of erythropoiesis is detected at the pre-MegE stage and remains suppressed through terminal reticulocyte differentiation. IL1 signals, exclusively, through the IL1 receptor (IL1R1). Using reciprocal transplants and mixed chimera experiments we demonstrate that IL1R1 expression in hematopoietic cells is completely dispensable for IL1-driven neutrophil production. Instead, IL1 acts on stromal cells to increase neutrophil production and diminish lymphocyte and erythrocyte production. Our analyses revealed that, in the stroma, only LepR+ perivascular cells and endothelial cells express IL1R1. Conditional Il1r1 deletion in LepR+ cells did not abrogate any of the hematopoietic phenotypes. However, conditional Il1r1 deletion in endothelial cells completely abrogated neutrophil production but did not prevent loss of erythroid and lymphoid lineages. Differentiation analyses showed that, after exposure to IL1, endothelial cells force the differentiation of immature, unipotent, neutrophil progenitors into terminally differentiated neutrophils. These studies thus demonstrate that endothelial cells provide a niche that is indispensable for neutrophil production during EG. This endothelial niche also uncouples neutrophil production from suppression of other hematopoietic lineages opening the door to targeting this pathway to selectively regulate neutropoiesis. Finally these data also highlight the bidirectional communication between the vascular niche and bone marrow neutrophils during stress. Bowers E, Slaughter A, Frenette PS, Kuick R, Pello OM, Lucas D. Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow. Nat Med. 2018;24:95-102 Disclosures No relevant conflicts of interest to declare.

scholarly journals Tie2+ Endothelial Cells Mediate Hematopoietic Stem Cell Regeneration Via EGF Signaling

2011 ◽  
Vol 17 (2) ◽  
pp. S188
Author(s):  
P.L. Doan ◽  
J.L. Russell ◽  
H.A. Himburg ◽  
K. Helms ◽  
S.K. Meadows ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Regeneration ◽  
Hematopoietic Stem ◽  
Egf Signaling

scholarly journals HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis

2021 ◽  
Author(s):  
Kaosheng Lv ◽  
Chujie Gong ◽  
Charles Antony ◽  
Xu Han ◽  
Jian-Gang Ren ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Ribosome Assembly ◽  
Cell Regeneration ◽  
Hematopoietic Stem
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