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https://www.readbyqxmd.com/read/28416717/essential-neuroscience-in-immunology
#1
REVIEW
Sangeeta S Chavan, Kevin J Tracey
The field of immunology is principally focused on the molecular mechanisms by which hematopoietic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416284/distinct-roles-for-matrix-metalloproteinases-2-and-9-in-embryonic-hematopoietic-stem-cell-emergence-migration-and-niche-colonization
#2
Lindsay N Theodore, Elliott J Hagedorn, Mauricio Cortes, Kelsey Natsuhara, Sarah Y Liu, Julie R Perlin, Song Yang, Madeleine L Daily, Leonard I Zon, Trista E North
Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically, the cellular mechanism(s) allowing HSPC egress and migration to secondary niches are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation-responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular interactions, and signaling. Here, inhibition of vascular-associated Mmp2 function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb(+) HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling...
April 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28413023/a-chemoattractant-guided-walk-through-lymphopoiesis-from-hematopoietic-stem-cells-to-mature-b-lymphocytes
#3
Vivian Y Lim, Sandra Zehentmeier, Chris Fistonich, João P Pereira
B lymphocytes develop from hematopoietic stem cells (HSCs) in specialized bone marrow niches composed of rare mesenchymal lineage stem/progenitor cells (MSPCs) and sinusoidal endothelial cells. These niches are defined by function and location: MSPCs are mostly perisinusoidal cells that together with a small subset of sinusoidal endothelial cells express stem cell factor, interleukin-7 (IL-7), IL-15, and the highest amounts of CXCL12 in bone marrow. Though rare, MSPCs are morphologically heterogeneous, highly reticular, and form a vast cellular network in the bone marrow parenchyma capable of interacting with large numbers of hematopoietic cells...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28406754/spheroid-coculture-of-hematopoietic-stem-progenitor-cells-and-monolayer-expanded-mesenchymal-stem-stromal-cells-in-polydimethylsiloxane-microwells-modestly-improves-in-vitro-hematopoietic-stem-progenitor-cell-expansion
#4
Kathryn Futrega, Kerry Atkinson, William B Lott, Michael R Doran
While two-dimensional (2D) monolayers of mesenchymal stem/stromal cells (MSCs) have been shown to enhance hematopoietic stem/progenitor cell (HSPC) expansion in vitro, expanded cells do not engraft long term in human recipients. This outcome is attributed to the failure of 2D culture to recapitulate the bone marrow (BM) niche signal milieu. Herein, we evaluated the capacity of a novel three-dimensional (3D) coculture system to support HSPC expansion in vitro. A high-throughput polydimethylsiloxane (PDMS) microwell platform was used to manufacture thousands of uniform 3D multicellular coculture spheroids...
April 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28401096/regulation-of-the-embryonic-erythropoietic-niche-a-future-perspective
#5
REVIEW
Ayako Yumine, Stuart T Fraser, Daisuke Sugiyama
The production of red blood cells, termed erythropoiesis, occurs in two waves in the developing mouse embryo: first primitive erythropoiesis followed by definitive erythropoiesis. In the mouse embryo, both primitive and definitive erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave then migrates to the fetal liver, fetal spleen and fetal bone marrow as these organs form. The fetal liver serves as the major organ for hematopoietic cell expansion and erythroid maturation after mid-gestation...
March 2017: Blood Research
https://www.readbyqxmd.com/read/28400375/continuous-blockade-of-cxcr4-results-in-dramatic-mobilization-and-expansion-of-hematopoietic-stem-and-progenitor-cells
#6
Darja Karpova, Julie Ritchey, Matthew Holt, Grazia Abou-Ezzi, Darlene Monlish, Lena Batoon, Susan Millard, Gabriele Spohn, Eliza Wiercinska, Ezhil Chendamarai, Will Yang, Stephanie Christ, Leah Gehrs, Laura G Schuettpelz, Klaus Dembowsky, Allison R Pettit, Michael Rettig, Halvard Boenig, John F DiPersio
Interaction between the chemokine receptor CXCR4 and its chief ligand CXCL12 plays a critical role in the retention and migration of hematopoietic stem and progenitor cells (HSPC) in the bone marrow (BM) microenvironment. In this study, qualitative and quantitative effects of long-term pharmacologic inhibition of the CXCR4/CXCL12 axis on the HSPC compartment were investigated using three structurally unrelated small molecule CXCR4 antagonists. A >10-fold increase in mobilization efficiency was achieved by applying the antagonists as subcutaneous continuous infusion for two weeks compared to single bolus injection...
April 11, 2017: Blood
https://www.readbyqxmd.com/read/28394335/progenitor-t-cell-differentiation-from-hematopoietic-stem-cells-using-delta-like-4-and-vcam-1
#7
Shreya Shukla, Matthew A Langley, Jastaranpreet Singh, John M Edgar, Mahmood Mohtashami, Juan Carlos Zúñiga-Pflücker, Peter W Zandstra
The molecular and cellular signals that guide T-cell development from hematopoietic stem and progenitor cells (HSPCs) remain poorly understood. The thymic microenvironment integrates multiple niche molecules to potentiate T-cell development in vivo. Recapitulating these signals in vitro in a stromal cell-free system has been challenging and limits T-cell generation technologies. Here, we describe a fully defined engineered in vitro niche capable of guiding T-lineage development from HSPCs. Synergistic interactions between Notch ligand Delta-like 4 and vascular cell adhesion molecule 1 (VCAM-1) were leveraged to enhance Notch signaling and progenitor T-cell differentiation rates...
April 10, 2017: Nature Methods
https://www.readbyqxmd.com/read/28381439/tumor-stroma-interactions-in-bone-metastasis-molecular-mechanisms-and-therapeutic-implications
#8
Hanqiu Zheng, Wenyang Li, Yibin Kang
Metastasis and associated complications are the major cause of death for cancer patients. The incidence of bone metastasis is among the highest in cancers arising from breast, prostate, and lung. Common skeletal-related events caused by bone metastasis include aberrant bone remodeling (osteolytic, osteoblastic, and mixed), bone pain, fracture, spinal cord compression, and life-threatening hypercalcemia. It is now known that interactions between tumor cells and bone stroma lie at the core of major steps of bone-metastasis progression...
April 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28375987/hematopoietic-stem-cells-under-pressure
#9
Miguel Ganuza, Shannon McKinney-Freeman
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation, and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT). Here, we focus on the physiological and molecular bottlenecks overcome by HSCs during transplantation...
April 1, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28363872/novel-therapeutic-strategies-to-target-leukemic-cells-that-hijack-compartmentalized-continuous-hematopoietic-stem-cell-niches
#10
REVIEW
Vashendriya V V Hira, Cornelis J F Van Noorden, Hetty E Carraway, Jaroslaw P Maciejewski, Remco J Molenaar
Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes...
March 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28362378/combining-intravital-fluorescent-microscopy-ivfm-with-genetic-models-to-study-engraftment-dynamics-of-hematopoietic-cells-to-bone-marrow-niches
#11
Lin Wang, Malgorzata M Kamocka, Amy Zollman, Nadia Carlesso
Increasing evidence indicates that normal hematopoiesis is regulated by distinct microenvironmental cues in the BM, which include specialized cellular niches modulating critical hematopoietic stem cell (HSC) functions(1)(,)(2). Indeed, a more detailed picture of the hematopoietic microenvironment is now emerging, in which the endosteal and the endothelial niches form functional units for the regulation of normal HSC and their progeny(3)(,)(4)(,)(5). New studies have revealed the importance of perivascular cells, adipocytes and neuronal cells in maintaining and regulating HSC function(6)(,)(7)(,)(8)...
March 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28351983/cxcr1-remodels-the-vascular-niche-to-promote-hematopoietic-stem-and-progenitor-cell-engraftment
#12
Bradley W Blaser, Jessica L Moore, Elliott J Hagedorn, Brian Li, Raquel Riquelme, Asher Lichtig, Song Yang, Yi Zhou, Owen J Tamplin, Vera Binder, Leonard I Zon
The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Recent advances marking fluorescent HSPCs have allowed exquisite visualization of HSPCs in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Here, we show that the chemokine cxcl8 and its receptor, cxcr1, are expressed by zebrafish endothelial cells, and we identify cxcl8/cxcr1 signaling as a positive regulator of HSPC colonization. Single-cell tracking experiments demonstrated that this is a result of increases in HSPC-endothelial cell "cuddling," HSPC residency time within the CHT, and HSPC mitotic rate...
April 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28348230/deficiency-of-transcription-factor-relb-perturbs-myeloid-and-dc-development-by-hematopoietic-extrinsic-mechanisms
#13
Carlos G Briseño, Marco Gargaro, Vivek Durai, Jesse T Davidson, Derek J Theisen, David A Anderson, Deborah V Novack, Theresa L Murphy, Kenneth M Murphy
RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB-inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe reduction of cDCs in Relb(-/-) mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type and Relb(-/-) bone marrow showed that RelB exerts cell-extrinsic actions on some lineages, but it has remained unclear whether the impact of RelB on cDC development is cell-intrinsic or -extrinsic...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28335858/netting-novel-regulators-of-hematopoiesis-and-hematologic-malignancies-in-zebrafish
#14
Wanda Kwan, Trista E North
Zebrafish are one of the preeminent model systems for the study of blood development (hematopoiesis), hematopoietic stem and progenitor cell (HSPC) biology, and hematopathology. The zebrafish hematopoietic system shares strong similarities in functional populations, genetic regulators, and niche interactions with its mammalian counterparts. These evolutionarily conserved characteristics, together with emerging technologies in live imaging, compound screening, and genetic manipulation, have been employed to successfully identify and interrogate novel regulatory mechanisms and molecular pathways that guide hematopoiesis...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28330582/adipocyte-accumulation-in-the-bone-marrow-during-obesity-and-aging-impairs-stem-cell-based-hematopoietic-and-bone-regeneration
#15
Thomas H Ambrosi, Antonio Scialdone, Antonia Graja, Sabrina Gohlke, Anne-Marie Jank, Carla Bocian, Lena Woelk, Hua Fan, Darren W Logan, Annette Schürmann, Luis R Saraiva, Tim J Schulz
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation...
March 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28319044/fibroblastic-niches-prime-t-cell-alloimmunity-through-delta-like-notch-ligands
#16
Jooho Chung, Christen L Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R Blazar, Alex Y Huang, Todd V Brennan, D Keith Bishop, Burkhard Ludewig, Christian W Siebel, Freddy Radtke, Sanjiv A Luther, Ivan Maillard
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28303517/vascular-and-perivascular-niches-but-not-the-osteoblastic-niche-are-numerically-restored-following-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aplastic-anemia
#17
Liangliang Wu, Wenjian Mo, Yuping Zhang, Ming Zhou, Yumiao Li, Ruiqing Zhou, Shiling Xu, Shiyi Pan, Hui Deng, Ping Mao, Shunqing Wang
Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells...
March 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28300168/zebrafish-caudal-haematopoietic-embryonic-stromal-tissue-chest-cells-support-haematopoiesis
#18
Anja Wolf, Julian Aggio, Clyde Campbell, Francis Wright, Gabriel Marquez, David Traver, David L Stachura
Haematopoiesis is an essential process in early vertebrate development that occurs in different distinct spatial locations in the embryo that shift over time. These different sites have distinct functions: in some anatomical locations specific hematopoietic stem and progenitor cells (HSPCs) are generated de novo. In others, HSPCs expand. HSPCs differentiate and renew in other locations, ensuring homeostatic maintenance. These niches primarily control haematopoiesis through a combination of cell-to-cell signalling and cytokine secretion that elicit unique biological effects in progenitors...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297579/endothelial-cells-promote-expansion-of-long-term-engrafting-marrow-hematopoietic-stem-and-progenitor-cells-in-primates
#19
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28292847/human-umbilical-cord-blood-borne-fibroblasts-contain-marrow-niche-precursors-that-form-a-bone-marrow-organoid-in-vivo
#20
Alice Pievani, Benedetto Sacchetti, Alessandro Corsi, Benedetta Rambaldi, Samantha Donsante, Valeria Scagliotti, Patrizia Vergani, Cristina Remoli, Andrea Biondi, Pamela G Robey, Mara Riminucci, Marta Serafini
Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche...
March 15, 2017: Development
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