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Hematopoietic niche

Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Taner Demirer
Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research...
March 20, 2018: Advances in Experimental Medicine and Biology
Wen Hao Neo, Christopher A G Booth, Emanuele Azzoni, Lijun Chi, Paul Delgado-Olguín, Marella F T R de Bruijn, Sten Eirik W Jacobsen, Adam J Mead
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 -inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 -inactivation resulted in embryonic lethality with severe anemia at E13...
March 19, 2018: Blood
Karin Kohlstedt, Caroline Trouvain, Timo Frömel, Thomas Mudersbach, Reinhard Henschler, Ingrid Fleming
In addition to being a peptidase, the angiotensin-converting enzyme (ACE) can be phosphorylated and involved in signal transduction. We evaluated the role of ACE in granulocyte-colony-stimulating factor (G-CSF)-induced hematopoietic progenitor cell (HPC) mobilization and detected a significant increase in mice-lacking ACE. Transplantation experiments revealed that the loss of ACE in the HPC microenvironment rather than in the HPCs increased mobilization. Indeed, although ACE was expressed by a small population of bone-marrow cells, it was more strongly expressed by endosteal bone...
March 17, 2018: Basic Research in Cardiology
Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, Toshiyuki Takai
Plasma cells (PCs) acquiring with long lives in bone marrow (BM) play a pivotal role in the humoral arm of immunological memory. The PCs reside in a special BM niche and produce antibodies against past-encountered pathogens or vaccine components for a long time. In BM, cysteine-X-cysteine (CXC) chemokine receptor type 4-expressing PCs and myeloid cells such as dendritic cells are attracted to and held by CXC chemokine ligand 12-secreting stromal cells, where survival of the PCs is supported by soluble factors such as IL-6 and a proliferation-inducing ligand or APRIL produced by neighboring myeloid cells...
February 24, 2018: International Immunology
Maile K Hollinger, Valentina Giudice, Nicole A Cummings, Guillermo Rivell, Hansheng Zhang, Sachiko Kajigaya, Keyvan Keyvanfar, Jichun Chen, Xingmin Feng, Neal S Young
While PD-1 blockade has revolutionized cancer immunotherapy, immune-related adverse events (irAEs) present life-threatening complications. Recent reports of aplastic anemia (AA) as irAEs implicate PD-1/PD-L1 as important in preventing immune-mediated destruction of the hematopoietic niche. Infusion of PD-1-deficient (PD-1 KO) lymph node (LN) cells into minor-antigen mismatched mice resulted in early mortality, as well as more severe BM hypoplasia, anemia, and BM microarchitecture disruption in PD-1 KO LN-infused mice relative to mice that received B6 LN cell infusion...
March 7, 2018: Experimental Hematology
Pingnan Xiao, Monika Dolinska, Lakshmi Sandhow, Makoto Kondo, Anne-Sofie Johansson, Thibault Bouderlique, Ying Zhao, Xidan Li, Marios Dimitriou, George Z Rassidakis, Eva Hellström-Lindberg, Nagahiro Minato, Julian Walfridsson, David T Scadden, Mikael Sigvardsson, Hong Qian
Mutations of signal-induced proliferation-associated gene 1 ( SIPA1 ), a RAP1 GTPase-activating protein, were reported in patients with juvenile myelomonocytic leukemia, a childhood myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Sipa1 deficiency in mice leads to the development of age-dependent MPN. However, Sipa1 expression in bone marrow (BM) microenvironment and its effect on the pathogenesis of MPN remain unclear. We here report that Sipa1 is expressed in human and mouse BM stromal cells and downregulated in these cells from patients with MPN or MDS/MPN at diagnosis...
March 13, 2018: Blood Advances
Bin Zhang, Le Xuan Truong Nguyen, Ling Li, Dandan Zhao, Bijender Kumar, Herman Wu, Allen Lin, Francesca Pellicano, Lisa Hopcroft, Yu-Lin Su, Mhairi Copland, Tessa L Holyoake, Calvin J Kuo, Ravi Bhatia, David S Snyder, Haris Ali, Anthony S Stein, Casey Brewer, Huafeng Wang, Tinisha McDonald, Piotr Swiderski, Estelle Troadec, Ching-Cheng Chen, Adrienne Dorrance, Vinod Pullarkat, Yate-Ching Yuan, Danilo Perrotti, Nadia Carlesso, Stephen J Forman, Marcin Kortylewski, Ya-Huei Kuo, Guido Marcucci
Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR-ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals...
March 5, 2018: Nature Medicine
O Kos, C Alexander, K Brandenburg, Z Chen, A Heini, D Heumann, I Khatri, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, T Waelli, K Yu, U Zähringer, R M Gorczynski
We have shown that an altered tissue redox environment in mice lacking either murine beta Hemoglobin major (Hgbβma KO) or minor (Hgbβmi KO) regulates inflammation. The REDOX environment in marrow stem cell niches also control differentiation pathways. We investigated osteoclastogenesis (OC)/osteoblastogenesis (OB), in bone cultures derived from untreated or FSLE-treated WT, Hgbβma KO or Hgbβmi KO mice. Marrow mesenchymal cells from 10d pre-cultures were incubated on an osteogenic matrix for 21d prior to analysis of inflammatory cytokine release into culture supernatants, and relative OC:OB using (TRAP:BSP, RANKL:OPG) mRNA expression ratios and TRAP or Von Kossa staining...
February 22, 2018: International Immunopharmacology
Florence Zylbersztejn, Mario Flores-Violante, Thibault Voeltzel, Franck-Emmanuel Nicolini, Sylvain Lefort, Véronique Maguer-Satta
The microenvironment (niche) governs the fate of stem cells (SC) by balancing self-renewal and differentiation. Increasing evidence indicates that the tumor niche plays an active role in cancer but its (important) properties for tumor initiation progression and resistance remain to be identified. Clinical data show that leukemic stem cells (LSC) survival is responsible for disease persistence and drug resistance probably due to their sustained interactions with the tumor niche. The Bone Morphogenetic Protein (BMP) signaling is a key pathway controlling stem cells and their niche, such as BMP2 and BMP4 important in both normal and cancer context...
February 22, 2018: Experimental Hematology
Yookyung Jung, Joel A Spencer, Anthony P Raphael, Juwell W Wu, Clemens Alt, Judith R Runnels, Briaira Geiger, Charles P Lin
The bone marrow is a unique microenvironment where blood cells are produced and released into the circulation. At the top of the blood cell lineage are the hematopoietic stem cells (HSC), which are thought to reside in close association with the bone marrow vascular endothelial cells (Morrison and Scadden, Nature 505:327-334, 2014). Recent efforts at characterizing the HSC niche have prompted us to make close examinations of two distinct types of blood vessel in the bone marrow, the arteriolar vessels originating from arteries and sinusoidal vessels connected to veins...
2018: Methods in Molecular Biology
Rahul Kumar, P Sonika Godavarthy, Daniela S Krause
The bone marrow microenvironment (BMM) is the 'domicile' of hematopoietic stem cells, as well as of malignant processes that can develop there. Multiple and complex interactions with the BMM influence hematopoietic stem cell (HSC) physiology, but also the pathophysiology of hematological malignancies. Reciprocally, hematological malignancies alter the BMM, in order to render it more hospitable for malignant progression. In this Cell Science at a Glance article and accompanying poster, we highlight concepts of the normal and malignant hematopoietic stem cell niches...
February 22, 2018: Journal of Cell Science
Stephen T Reece, Alexis Vogelzang, Julia Tornack, Wolfgang Bauer, Ulrike Zedler, Sandra Schommer-Leitner, Georg Stingl, Fritz Melchers, Stefan H E Kaufmann
Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M...
February 17, 2018: Journal of Infectious Diseases
Aline F Ferreira, George A Calin, Virgínia Picanço-Castro, Simone Kashima, Dimas T Covas, Fabiola A de Castro
Although hematopoietic stem cell (HSC) therapy for hematological diseases can lead to a good outcome from the clinical point of view, the limited number of ideal donors, the comorbidity of patients and the increasing number of elderly patients may limit the application of this therapy. HSCs can be generated from induced pluripotent stem cells (iPSCs), which requires the understanding of the bone marrow and liver niches components and function in vivo iPSCs have been extensively applied in several studies involving disease models, drug screening and cellular replacement therapies...
February 21, 2018: Journal of Cell Science
Sarah K Tasian, Martin Bornhäuser, Sergio Rutella
Abst ract: The bone marrow (BM) niche encompasses multiple cells of mesenchymal and hematopoietic origin and represents a unique microenvironment that is poised to maintain hematopoietic stem cells. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the BM hosts various mature lymphoid cell types, including naïve T cells, memory T cells and plasma cells, as well as mature myeloid elements such as monocyte/macrophages and neutrophils, all of which are crucially important to control leukemia initiation and progression...
February 21, 2018: Biomedicines
Cong Wang, Yan Yang, Sujun Gao, Jingcheng Chen, Jinyuan Yu, Han Zhang, Mingxi Li, Xingying Zhan, Wei Li
Myelodysplastic syndrome (MDS) is a heterogeneous hematological malignancy, characterized by cytopenia and accompanied by a risk of transformation into acute myeloid leukemia (AML). Epidemiological studies for decades have shown association between autoimmune diseases (AIDs) and MDS. Specifically, patients with antecedent AIDs tends to have an increased risk of developing MDS, and these patients display different clinical characteristics and outcomes. Importantly, immune dysregulation has been the common driving force between MDS and AIDs pathogenesis...
February 2018: Critical Reviews in Oncology/hematology
Yuichi Hirata, Kazuhiro Furuhashi, Hiroshi Ishii, Hao Wei Li, Sandra Pinho, Lei Ding, Simon C Robson, Paul S Frenette, Joji Fujisaki
A crucial player in immune regulation, FoxP3+ regulatory T cells (Tregs) are drawing attention for their heterogeneity and noncanonical functions. Here, we describe a Treg subpopulation that controls hematopoietic stem cell (HSC) quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150, and localized within the HSC niche in the bone marrow (BM). Specific reduction of BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche Tregs protected HSCs from oxidative stress and maintained HSC quiescence...
February 7, 2018: Cell Stem Cell
Sandra Pinho, Tony Marchand, Eva Yang, Qiaozhi Wei, Claus Nerlov, Paul S Frenette
The spatial localization of hematopoietic stem cells (HSCs) in the bone marrow (BM) remains controversial, with some studies suggesting that they are maintained in homogeneously distributed niches while others have suggested the contributions of distinct niche structures. Subsets of quiescent HSCs have been reported to associate with megakaryocytes (MK) or arterioles in the BM. However, these HSC subsets have not been prospectively defined. Here, we show that platelet and myeloid-biased HSCs, marked by von Willebrand factor (vWF) expression, are highly enriched in MK niches...
February 9, 2018: Developmental Cell
Ander Abarrategi, Syed A Mian, Diana Passaro, Kevin Rouault-Pierre, William Grey, Dominique Bonnet
Xenotransplantation of patient-derived samples in mouse models has been instrumental in depicting the role of hematopoietic stem and progenitor cells in the establishment as well as progression of hematological malignancies. The foundations for this field of research have been based on the development of immunodeficient mouse models, which provide normal and malignant human hematopoietic cells with a supportive microenvironment. Immunosuppressed and genetically modified mice expressing human growth factors were key milestones in patient-derived xenograft (PDX) models, highlighting the importance of developing humanized microenvironments...
February 16, 2018: Journal of Experimental Medicine
Martin Breitbach, Kenichi Kimura, Tiago C Luis, Christopher J Fuegemann, Petter S Woll, Michael Hesse, Raffaella Facchini, Sarah Rieck, Katarzyna Jobin, Julia Reinhardt, Osamu Ohneda, Daniela Wenzel, Caroline Geisen, Christian Kurts, Wolfgang Kastenmüller, Michael Hölzel, Sten E W Jacobsen, Bernd K Fleischmann
Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP+ MSCs in various organs. In vivo, EGFP+ mesenchymal cells were observed in fetal and adult bones at proliferative ossification sites, while in solid organs EGFP+ cells exhibited a perivascular distribution pattern. EGFP+ cells from the bone compartment could be clonally expanded ex vivo from single cells and displayed trilineage differentiation potential...
February 1, 2018: Cell Stem Cell
Herbert Strobl, Corinna Krump, Izabela Borek
Human Langerhans cells (LC) can be generated ex vivo from hematopoietic precursor cells in response to cytokines and cell-membrane associated ligands. These in vitro differentiation models provided mechanistic insights into the molecular and cellular pathways underlying the development of this unique, epithelia-associated dendritic cell subset. Notably, the human epidermal microenvironment is fully sufficient to induce LC differentiation from hematopoietic progenitors. Hence, dissecting the molecular characteristics of the human epithelial/epidermal LC niche, and testing defined ligands for their capacity to induce LC differentiation, led to a refined molecular model of LC lineage commitment...
February 12, 2018: Seminars in Cell & Developmental Biology
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