Bone marrow adipocytes support hematopoietic stem cell survival

2017 ◽  
Vol 233 (2) ◽  
pp. 1500-1511 ◽  
Author(s):  
Domenico Mattiucci ◽  
Giulia Maurizi ◽  
Valerio Izzi ◽  
Lorenzo Cenci ◽  
Marco Ciarlantini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cell Survival ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Bone Marrow Adipocytes ◽  
Stem Cell Survival

scholarly journals Prostaglandin E2 Increases Hematopoietic Stem Cell Survival and Accelerates Hematopoietic Recovery After Radiation Injury

Stem Cells ◽  
2013 ◽  
Vol 31 (2) ◽  
pp. 372-383 ◽  
Author(s):  
Rebecca L. Porter ◽  
Mary A. Georger ◽  
Olga Bromberg ◽  
Kathleen E. McGrath ◽  
Benjamin J. Frisch ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prostaglandin E2 ◽  
Cell Survival ◽  
Hematopoietic Stem Cell ◽  
Radiation Injury ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Stem Cell Survival

scholarly journals Pontin is essential for murine hematopoietic stem cell survival

Haematologica ◽  
2012 ◽  
Vol 97 (9) ◽  
pp. 1291-1294 ◽  
Author(s):  
O. Bereshchenko ◽  
E. Mancini ◽  
L. Luciani ◽  
A. Gambardella ◽  
C. Riccardi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem Cell Survival ◽  
Murine Hematopoietic Stem Cell

scholarly journals UFMylation of MRE11 is essential for maintenance of telomere length and hematopoietic stem cell survival

2019 ◽  
Author(s):  
Lara Lee ◽  
Ana Belen Perez Oliva ◽  
Dmitri Churikov ◽  
Elena Martinez-Balsalobre ◽  
Joshua Peter ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Telomere Length ◽  
Hematopoietic Stem Cell ◽  
Strand Break ◽  
Telomere Maintenance ◽  
Hematopoietic Stem ◽  
Telomere Protein ◽  
Stem Cell Survival

AbstractGenetic studies using knockout mouse models provide strong evidence for the essential role of the ubiquitin-like protein UFM1 for hematopoiesis, especially erythroid development, yet its biological roles in this process are largely unknown. Here we have identified a UFL1-dependent UFMylation of the MRE11 nuclease on the K281 and K282 residues. We show that Hela cells lacking the specific UFM1 E3 ligase display severe telomere shortening. We further demonstrate either by deleting UFM1 or by mutating MRE11 UFMylation sites that preventing MRE11 UFMylation impacts its interaction with the telomere protein TRF2. However, the MRE11 function in double-strand-break repair remains intact. We validate these results in vivo by showing that Zebrafish knockouts for the genes ufl1 and ufm1 have shorter telomeres in hematopoietic cells. Here we present UFMylation has a new mechanisms of regulation for telomere length maintenance with a role in hematopoiesis.Key pointsModification of MRE11 by UFM1 regulates telomere maintenance and cell death in HSCsScientific categoryUFMylation, telomere maintenance, hematopoietic stem cell survival.

Cultured Human Macrophages As a Model for Central Macrophages in Erythroblastic Islands

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1248-1248
Author(s):  
Esther Heideveld ◽  
Maartje van Den Biggelaar ◽  
Floris P. van Alphen ◽  
Marieke Von Lindern ◽  
Emile van den Akker
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cell Survival ◽  
Peripheral Blood ◽  
Human Bone ◽  
Hematopoietic Stem ◽  
Erythroblastic Island ◽  
Stem Cell Survival

Abstract Erythropoiesis occurs in erythroblastic islands, specific structures in the bone marrow comprising a central macrophage surrounded by erythroid precursors at different stages of terminal differentiation. The central macrophage of the erythroblastic island supports proliferation and differentiation of erythroblasts, as well as phagocytosis of the extruded erythroblast nuclei, the pyrenocytes. Its identity, however, has been poorly characterized. We previously showed that macrophages also enhance in vitro erythropoiesis because they support hematopoietic stem cell (HSC) survival [Heideveld et al. 2015]. Thus, bone marrow macrophages affect all stages of erythropoiesis. The aim of our study is to characterize the relevant human bone marrow macrophages and unravel the mechanism by which they support erythropoiesis with the ultimate goal (i) to optimize erythroblast culture systems that produce erythrocytes for transfusion purposes, and (ii) to target macrophages in vivo to improve erythropoiesis in anemic patients. Macrophages are a heterogeneous population, that can be divided into pro-inflammatory M1 and anti-inflammatory M2 macrophages. Macrophages that we showed to support stem cell survival, and subsequently enhance the yield of erythroid cell cultures, were characterized as a subclass: M2c-like macrophages. These macrophages were derived from CD14+ cells isolated from human peripheral blood mononuclear cells that were cultured in serum-free media supplemented with stem cell factor, erythropoietin and dexamethasone. Within three days these macrophages expressed CD163high, CD169, mannose receptor (MR), CXCR4 and HLA-DR and harbored characteristics of bone marrow resident macrophages. This differentiation process was dependent on glucocorticoid receptor activation. Mass spectrometry of monocytes cultured in presence and absence of dexamethasone showed that expression of CD163 and MR was strictly Dex-dependent, underscoring the role of glucocorticoids in the phenotype of M2c macrophages. Protein ontology analysis revealed dexamethasone-mediated enrichment of lysosome, endocytosis and endothelial development (e.g. STAB1, IL13RA1, CD81, SLC1A3 and FKBP5). We wondered whether these macrophages with increased endosomal and lysosomal capacity not only support stem cell survival and enable erythroid commitment, but also support erythroblastic islands. In mice, it has been shown that clearance of the pyrenocytes by central macrophages occurs presumably via TAM-receptors on the macrophages. Indeed, mRNA expression of cultured M2c-like macrophages showed increased levels of TAM family members MerTK and AXL. Functionally, these macrophages have the capacity to phagocytose zymosan and to bind nuclei. Furthermore, co-culture of the M2c-like macrophages with erythroblasts yielded GPA+(erythroid marker)/CD14+ cell aggregates that suggested the formation of erythroblastic islands. Interestingly, M2c-like macrophages expressing CD163high, MR and CD169 were also observed in human bone marrow aspirates and human fetal livers resembling macrophages induced in in vitro cultures in presence of dexamethasone. Currently, we investigate the mechanism by which glucocorticoids induce monocytes to differentiate into macrophages that may be used to model erythroblastic island-mediated erythropoiesis. Knowledge on the function of such a erythroblastic island is lacking by the absence of an in vitro model. Furthermore, targeting this mechanism in vivo may enhance the recovery of erythropoiesis following bone marrow transplantation. CD14+ cells from peripheral blood positively regulate hematopoietic stem and progenitor cell survival resulting in increased erythroid yield. (2015) Heideveld E, Masiello F, Marra M, Esteghamat F, Yağcı N, von Lindern M, Migliaccio AR, van den Akker E. Haematologica. 100(11):1396-1406 Disclosures No relevant conflicts of interest to declare.

scholarly journals Gata2 −77 enhancer regulates adult hematopoietic stem cell survival

Leukemia ◽  
2020 ◽  
Author(s):  
Xiaona You ◽  
Yuan-I Chang ◽  
Guangyao Kong ◽  
Erik A. Ranheim ◽  
Yun Zhou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem Cell Survival

scholarly journals UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival

2021 ◽  
Vol 7 (39) ◽  
Author(s):  
Lara Lee ◽  
Ana Belen Perez Oliva ◽  
Elena Martinez-Balsalobre ◽  
Dmitri Churikov ◽  
Joshua Peter ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Telomere Length ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem Cell Survival

scholarly journals Bone Marrow Adipocytes: The Enigmatic Components of the Hematopoietic Stem Cell Niche

2019 ◽  
Vol 8 (5) ◽  
pp. 707 ◽  
Author(s):  
Vincent Cuminetti ◽  
Lorena Arranz
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Niche ◽  
Functional Responses ◽  
Hematopoietic Stem ◽  
Bone Marrow Adipocytes ◽  
Hematopoietic Stem Cell Niche ◽  
Cell Niche

Bone marrow adipocytes (BMA) exert pleiotropic roles beyond mere lipid storage and filling of bone marrow (BM) empty spaces, and we are only now beginning to understand their regulatory traits and versatility. BMA arise from the differentiation of BM mesenchymal stromal cells, but they seem to be a heterogeneous population with distinct metabolisms, lipid compositions, secretory properties and functional responses, depending on their location in the BM. BMA also show remarkable differences among species and between genders, they progressively replace the hematopoietic BM throughout aging, and play roles in a range of pathological conditions such as obesity, diabetes and anorexia. They are a crucial component of the BM microenvironment that regulates hematopoiesis, through mechanisms largely unknown. Previously considered as negative regulators of hematopoietic stem cell function, recent data demonstrate their positive support for hematopoietic stem cells depending on the experimental approach. Here, we further discuss current knowledge on the role of BMA in hematological malignancies. Early hints suggest that BMA may provide a suitable metabolic niche for the malignant growth of leukemic stem cells, and protect them from chemotherapy. Future in vivo functional work and improved isolation methods will enable determining the true essence of this elusive BM hematopoietic stem cell niche component, and confirm their roles in a range of diseases. This promising field may open new pathways for efficient therapeutic strategies to restore hematopoiesis, targeting BMA.

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