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Hematopoietic niche

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https://www.readbyqxmd.com/read/28729299/notch2-blockade-enhances-hematopoietic-stem-cell-mobilization-and-homing
#1
Weihuan Wang, Shuiliang Yu, Jay Myers, Yiwei Wang, William W Xin, Marwah Alkabri, Alison W Xin, Ming Li, Alex Y Huang, Wei Xin, Christian W Siebel, Hillard M Lazarus, Lan Zhou
Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation may mobilize limited numbers of hematopoietic progenitor cells into blood, precluding use of the procedure, or being placed at increased risk for complications due to slow hematopoietic reconstitution. Developing more efficacious hematopoietic progenitor cell mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is dispensable for homeostasis of adult hematopoietic stem cells, Notch-ligand adhesive interaction maintains hematopoietic stem cell quiescence and niche retention...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28714470/essential-role-of-fbxl5-mediated-cellular-iron-homeostasis-in-maintenance-of-hematopoietic-stem-cells
#2
Yoshiharu Muto, Masaaki Nishiyama, Akihiro Nita, Toshiro Moroishi, Keiichi I Nakayama
Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#3
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28702683/blood-on-the-tracks-hematopoietic-stem-cell-endothelial-cell-interactions-in-homing-and-engraftment
#4
REVIEW
Julie R Perlin, Audrey Sporrij, Leonard I Zon
Cells of the hematopoietic system undergo rapid turnover. Each day, humans require the production of about one hundred billion new blood cells for proper function. Hematopoietic stem cells (HSCs) are rare cells that reside in specialized niches and are required throughout life to produce specific progenitor cells that will replenish all blood lineages. There is, however, an incomplete understanding of the molecular and physical properties that regulate HSC migration, homing, engraftment, and maintenance in the niche...
August 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28688581/persistent-and-inducible-neogenesis-repopulates-progenitor-renin-lineage-cells-in-the-kidney
#5
Linda Hickmann, Anne Steglich, Michael Gerlach, Moath Al-Mekhlafi, Jan Sradnick, Peter Lachmann, Maria Luisa S Sequeira-Lopez, R Ariel Gomez, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
Renin lineage cells (RLCs) serve as a progenitor cell reservoir during nephrogenesis and after renal injury. The maintenance mechanisms of the RLC pool are still poorly understood. Since RLCs were also identified as a progenitor cell population in bone marrow we first considered that these may be their source in the kidney. However, transplantation experiments in adult mice demonstrated that bone marrow-derived cells do not give rise to RLCs in the kidney indicating their non-hematopoietic origin. Therefore we tested whether RLCs develop in the kidney through neogenesis (de novo differentiation) from cells that have never expressed renin before...
July 6, 2017: Kidney International
https://www.readbyqxmd.com/read/28687990/cd34-negative-hematopoietic-stem-cells-show-distinct-expression-profiles-of-homing-molecules-that-limit-engraftment-in-mice-and-sheep
#6
Tomoyuki Abe, Yoshikazu Matsuoka, Yoshikazu Nagao, Yoshiaki Sonoda, Yutaka Hanazono
We and others have reported that human hematopoietic stem cells (HSCs) are also present in the CD34-negative (CD34(-)) fraction of human cord blood (CB). Here, we examined the hematopoietic engraftment potential of 13 or 18 lineage-negative (13Lin(-) or 18Lin(-)) CD34(+/-) cells from human CB in mice and sheep. Both 13Lin(-) and 18Lin(-) CD34(+) cells efficiently engrafted in mice irrespective of transplantation route, be it by tail-vein injection (TVI) or by intra-bone marrow injection (IBMI). These cells also engrafted in sheep after in utero fetal intra-hepatic injection (IHI)...
July 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28676663/3d-models-of-the-hematopoietic-stem-cell-niche-under-steady-state-and-active-conditions
#7
Lisa Rödling, Ivo Schwedhelm, Saskia Kraus, Karen Bieback, Jan Hansmann, Cornelia Lee-Thedieck
Hematopoietic stem cells (HSCs) in the bone marrow are able to differentiate into all types of blood cells and supply the organism each day with billions of fresh cells. They are applied to cure hematological diseases such as leukemia. The clinical need for HSCs is high and there is a demand for being able to control and multiply HSCs in vitro. The hematopoietic system is highly proliferative and thus sensitive to anti-proliferative drugs such as chemotherapeutics. For many of these drugs suppression of the hematopoietic system is the dose-limiting toxicity...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673932/integrin-%C3%AE-v%C3%AE-3-enhances-the-suppressive-effect-of-interferon-%C3%AE-on-hematopoietic-stem-cells
#8
Terumasa Umemoto, Yu Matsuzaki, Yoshiko Shiratsuchi, Michihiro Hashimoto, Takayuki Yoshimoto, Ayako Nakamura-Ishizu, Brian Petrich, Masayuki Yamato, Toshio Suda
Hematopoietic homeostasis depends on the maintenance of hematopoietic stem cells (HSCs), which are regulated within a specialized bone marrow (BM) niche. When HSC sense external stimuli, their adhesion status may be critical for determining HSC cell fate. The cell surface molecule, integrin αvβ3, is activated through HSC adhesion to extracellular matrix and niche cells. Integrin β3 signaling maintains HSCs within the niche. Here, we showed the synergistic negative regulation of the pro-inflammatory cytokine interferon-γ (IFNγ) and β3 integrin signaling in murine HSC function by a novel definitive phenotyping of HSCs...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28670819/emerging-roles-of-transit-amplifying-cells-in-tissue-regeneration-and-cancer
#9
REVIEW
Bing Zhang, Ya-Chieh Hsu
Most regenerative tissues employ transit-amplifying cells (TACs) that are positioned in between stem cells and differentiated progeny. In a classical hierarchical model, stem cells undergo limited divisions to produce TACs, which then proliferate rapidly to expand the system and produce diverse differentiated cell types. Although TACs are indispensable for generating tissues, they have been largely viewed as a transit point between stem cells and downstream lineages. Studies in the past few years, however, have revealed some fascinating biology and unanticipated functions of TACs...
July 3, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28669077/lung-as-a-niche-for-hematopoietic-progenitors
#10
Isabella Borges, Isadora Sena, Patrick Azevedo, Julia Andreotti, Viviani Almeida, Ana Paiva, Gabryella Santos, Daniel Guerra, Pedro Prazeres, Luiza Lousado Mesquita, Luanny Souto de Barros Silva, Caroline Leonel, Akiva Mintz, Alexander Birbrair
Platelets are released from megakaryocytes. The bone marrow has been proposed to be the major site where this process occurs. Lefrançais et al. (2017) using state-of-the-art techniques including two-photon microscopy, in vivo lineage-tracing technologies, and sophisticated lung transplants reveal that the lung is also a primary site for platelet biogenesis. Strikingly, lung megakaryocytes can completely reconstitute platelet counts in the blood in mice with thrombocytopenia. This study also shows that hematopoietic progenitors, with capacity to repopulate the bone marrow after irradiation, are present in the lungs...
July 1, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28662672/fibroblast-growth-factor-2-supports-osteoblastic-niche-cells-during-hematopoietic-homeostasis-recovery-after-bone-marrow-suppression
#11
Kyung-Ae Yoon, YeonSung Son, Young-Jin Choi, Joo-Hyun Kim, Je-Yoel Cho
BACKGROUND: Hematopoietic stem cell (HSC) maintenance requires a specific microenvironment. HSC niches can be activated by tissue damaging chemotherapeutic drugs and various cell signaling molecules such as SDF-1 and FGF, which might also result in bone marrow stress. Recent research has insufficiently shown that endosteal osteolineage cells and other niche constituents recover after marrow injury. METHODS: We investigated the role of FGF2 in the osteoblastic niche cells during hematopoietic homeostasis recovery after bone marrow injury...
June 29, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28660376/bone-metabolism-markers-and-angiogenic-cytokines-as-regulators-of-human-hematopoietic-stem-cell-mobilization
#12
Pantelis Tsirkinidis, Evangelos Terpos, Georgios Boutsikas, Athanasios Papatheodorou, Konstantinos Anargyrou, Eleni Lalou, Aglaia Dimitrakopoulou, Christina Kalpadakis, Konstantinos Konstantopoulos, Marina Siakantaris, Panayiotis Panayiotidis, Gerassimos Pangalis, Marie-Christine Kyrtsonis, Theodoros Vassilakopoulos, Maria K Angelopoulou
Hematopoietic stem cell (HSC) mobilization involves cleavage of ligands between HSC and niche components. However, there are scarce data regarding the role of bone cells in human HSC mobilization. We studied biochemical markers of bone metabolism and angiogenic cytokines during HSC mobilization in 46 patients' sera with lymphoma and multiple myeloma, by ELISA. Significant changes between pre-mobilization and collection samples were found: (1) Bone alkaline phosphatase (BALP) increased, indicating augmentation of bone formation; (2) Receptor activator of Nf-κB ligand/osteoprotegerin ratio (RANKL/OPG) increased, showing osteoclastic differentiation and survival; however, there was no evidence of increased osteoclastic activity; and (3) Angiopoietin-1/Angiopoietin-2 ratio (ANGP-1/ANGP-2) decreased, consistent with vessel destabilization...
June 28, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28660186/use-of-imaging-techniques-to-illuminate-dynamics-of-hematopoietic-stem-cells-and-their-niches
#13
REVIEW
Takayuki Morikawa, Keiyo Takubo
Continuous generation of blood cells over an organism's lifetime is supported by hematopoietic stem/progenitor cells (HSPCs) capable of producing all hematopoietic cell subtypes. Adult mammalian HSPCs are localized to bone marrow and regulated by their neighboring microenvironment, or "niche." Because interactions of HSPCs with their niches are highly dynamic and complex, the recent development of imaging technologies provides a powerful new tool to understand stem cell/niche biology. In this review, we discuss recent advances in our understanding of dynamic HSPC/niche interactions during development, homeostasis, disease states or aging with a focus on studies advanced by imaging analysis...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28658717/bone-marrow-on-a-chip-long-term-culture-of-human-hematopoietic-stem-cells-in-a-3d-microfluidic-environment
#14
Stefan Sieber, Lorenz Wirth, Nino Cavak, Marielle Koenigsmark, Uwe Marx, Roland Lauster, Mark Rosowski
Multipotent hematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to this date no in vitro model exists that truthfully mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs. In this study, we present a novel 3D co-culture model, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic Multi-Organ-Chip (MOC)...
June 28, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28655551/adult-venous-endothelium-is-a-niche-for-highly-proliferative-and-vasculogenic-endothelial-colony-forming-cells
#15
Linden Green, Richard H Ofstein, Brian Rapp, M Reza Saadatzadeh, Janak R Bhavsar, Andres Fajardo, Michael C Dalsing, David A Ingram, Michael P Murphy
OBJECTIVE: Postnatal resident endothelium of blood vessels has been proposed to represent terminally differentiated tissue that does not replicate. We previously isolated endothelial colony-forming cells (ECFCs) from human umbilical cord blood (CB) and term placenta by using colony-forming assays and immunocytochemistry. We showed that ECFCs are highly proliferative and form functioning vessels in vivo, the defining characteristics of a true endothelial progenitor cell. This exploratory investigation was conducted to determine whether the endothelium of healthy adult blood vessels contained resident ECFCs...
June 24, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28642593/transforming-growth-factor-%C3%AE-1-regulates-the-nascent-hematopoietic-stem-cell-niche-by-promoting-gluconeogenesis
#16
C-Y Zhang, H-M Yin, H Wang, D Su, Y Xia, L-F Yan, B Fang, W Liu, Y-M Wang, A-H Gu, Y Zhou
The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-β1 in the metabolic niche of HSC emergence using the tgf-β1b(-/-) zebrafish. Our findings first showed that Tgf-β1 transcripts were enriched in the nascent HSCs. Loss of tgf-β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-β1b(+) cells were runx1(+) HSCs and underwent an endothelial-to-hematopoietic-transition process...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#17
REVIEW
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28639326/bone-marrow-hematons-an-access-point-to-the-human-hematopoietic-niche
#18
Alexandre Janel, Juliette Berger, Céline Bourgne, Richard Lemal, Nathalie Boiret-Dupré, Frédérique Dubois-Galopin, Pierre Déchelotte, Charlotte Bothorel, Eric Hermet, Sara Chabi, Jacques-Olivier Bay, Céline Lambert, Bruno Pereira, Françoise Pflumio, Rima Haddad, Marc G Berger
To understand the complex interactions between hematopoietic stem cells and the bone marrow niche, a human experimental model is needed. Our hypothesis is that hematons are an appropriate ex vivo model of human bone marrow. We analyzed the hierarchical hematopoietic cell content and the tissue organization of single hematons from healthy donors. Most (>90%) hematons contained precursors of all cell lineages, myeloid progenitors, and LTC-ICs without preferential commitment. Approximately half of the hematons could generate significant levels of lympho-myeloid hematopoiesis after transplantation in an NSG mouse model, despite the low absolute numbers of transplanted CD34(+) cells...
June 22, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28637883/niche-mediated-depletion-of-the-normal-hematopoietic-stem-cell-reservoir-by-flt3-itd-induced-myeloproliferation
#19
Adam J Mead, Wen Hao Neo, Nikolaos Barkas, Sahoko Matsuoka, Alice Giustacchini, Raffaella Facchini, Supat Thongjuea, Lauren Jamieson, Christopher A G Booth, Nicholas Fordham, Cristina Di Genua, Deborah Atkinson, Onima Chowdhury, Emmanouela Repapi, Nicki Gray, Shabnam Kharazi, Sally-Ann Clark, Tiphaine Bouriez, Petter Woll, Toshio Suda, Claus Nerlov, Sten Eirik W Jacobsen
Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs), FLT3 internal tandem duplications (FLT3 ITDs) have recently been suggested to intrinsically suppress HSCs. Herein, single-cell interrogation found Flt3 mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation between Flt3 and HSC-associated gene expression. Flt3-ITD knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28636974/sema3a-partially-reverses-vegf-effects-through-binding-to-neuropilin-1
#20
Bruna Palodetto, Adriana da Silva Santos Duarte, Matheus Rodrigues Lopes, Flavia Adolfo Corrocher, Fernanda Marconi Roversi, Fernanda Soares Niemann, Karla Priscila Vieira Ferro, Ana Leda Figueiredo Longhini, Paula Melo Campos, Patricia Favaro, Sara Teresinha Olalla Saad
Cross-talk between hematopoietic stem cells (HSCs) and bone marrow stromal cells (BMSCs) is essential for HSCs regulation and leukemogenesis. Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, we found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34(+) HSCs and semaphorin 3A (SEMA3A) in BMSCs. To better understand the role of VEGFA and SEMA3A in leukemogenesis, we recruited 30 myelodysplastic syndrome (MDS) patients, 29 acute myeloid leukemia (6 secondary to MDS) patients and 12 controls...
June 3, 2017: Stem Cell Research
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