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Donatella Bardelli, Erica Dander, Cristina Bugarin, Claudia Cappuzzello, Alice Pievani, Grazia Fazio, Paolo Pierani, Paola Corti, Piero Farruggia, Carlo Dufour, Simone Cesaro, Marco Cipolli, Andrea Biondi, Giovanna D'Amico
Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS-MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model...
May 16, 2018: British Journal of Haematology
Julia Scheinpflug, Moritz Pfeiffenberger, Alexandra Damerau, Franziska Schwarz, Martin Textor, Annemarie Lang, Frank Schulze
Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed...
May 10, 2018: Genes
Jianfeng Jiao, Min Luo, Ruiqi Wang
BACKGROUND: The haematopoietic lineages with leukaemia lineages are considered in this paper. In particular, we mainly consider that haematopoietic lineages are tightly controlled by negative feedback inhibition of end-product. Actually, leukemia has been found 100 years ago. Up to now, the exact mechanism is still unknown, and many factors are thought to be associated with the pathogenesis of leukemia. Nevertheless, it is very necessary to continue the profound study of the pathogenesis of leukemia...
April 24, 2018: BMC Systems Biology
Chen Zhu, Lixia Xia, Fei Li, Lingren Zhou, Qingyu Weng, Zhouyang Li, Yinfang Wu, Yuanyuan Mao, Chao Zhang, Yanping Wu, Miao Li, Songmin Ying, Zhihua Chen, Huahao Shen, Wen Li
Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis...
May 2, 2018: Scientific Reports
Rebecca S Lee, Andrew P Waters, James M Brewer
Blood stage human malaria parasites may exploit erythropoietic tissue niches and colonise erythroid progenitors; however, the precise influence of the erythropoietic environment on fundamental parasite biology remains unknown. Here we use quantitative approaches to enumerate Plasmodium infected erythropoietic precursor cells using an in vivo rodent model of Plasmodium berghei. We show that parasitised early reticulocytes (ER) in the major sites of haematopoiesis establish a cryptic asexual cycle. Moreover, this cycle is characterised by early preferential commitment to gametocytogenesis, which occurs in sufficient numbers to generate almost all of the initial population of circulating, mature gametocytes...
April 27, 2018: Nature Communications
Sergi Cuartero, Matthias Merkenschlager
PURPOSE OF REVIEW: The three-dimensional organization of the genome inside the nucleus impacts on key aspects of genome function, including transcription, DNA replication and repair. The chromosome maintenance complex cohesin and the DNA binding protein CTCF cooperate to drive the formation of self-interacting topological domains. This facilitates transcriptional regulation via enhancer-promoter interactions, controls the distribution and release of torsional strain, and affects the frequency with which particular translocations arise, based on the spatial proximity of translocation partners...
April 26, 2018: Current Opinion in Hematology
Kyunghee Choi
PURPOSE OF REVIEW: Recent studies have established that haematopoietic stem cells (HSCs) remain quiescent in homeostatic conditions, and minimally contribute to haematopoietic homeostasis. However, they undergo extensive cell cycle and expansion upon bone marrow transplantation or haematopoietic injury to reestablish the haematopoietic system. Molecular basis for the HSC activation and expansion is not completely understood. Here, we review the recent study elucidating the role of the developmentally critical Ets transcription factor Etv2 in reestablishing haematopoietic system upon injury through promoting HSC regeneration...
April 24, 2018: Current Opinion in Hematology
Roman Galeev, Jonas Larsson
PURPOSE OF REVIEW: Disturbance of the delicate balance between self-renewal and differentiation in haematopoietic stem cells (HSCs) can lead to both leukaemia and bone marrow failure. The regulation of this balance in HSC biology has been intensely investigated in several model systems, and lately the importance of epigenetic modifications as well as the organization and architecture of chromatin has become increasingly recognized. In this review, we will focus on the role of the chromatin organizing protein complex cohesin in regulation of normal and malignant haematopoiesis...
April 24, 2018: Current Opinion in Hematology
Nieves Peltzer, Maurice Darding, Antonella Montinaro, Peter Draber, Helena Draberova, Sebastian Kupka, Eva Rieser, Amanda Fisher, Ciaran Hutchinson, Lucia Taraborrelli, Torsten Hartwig, Elodie Lafont, Tobias L Haas, Yutaka Shimizu, Charlotta Böiers, Aida Sarr, James Rickard, Silvia Alvarez-Diaz, Michael T Ashworth, Allison Beal, Tariq Enver, John Bertin, William Kaiser, Andreas Strasser, John Silke, Philippe Bouillet, Henning Walczak
The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death2-8 . In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype9-11 ...
May 2018: Nature
Ankur Jain, Praveen Sharma, Alka Khadwal, Pankaj Malhotra
No abstract text is available yet for this article.
March 2018: Journal of Clinical Orthopaedics and Trauma
Bo Huang, Juntao Jiang, Bangwei Luo, Wen Zhu, Yuqi Liu, Zhishang Wang, Zhiren Zhang
Systemic lupus erythematosus (SLE) is an autoimmune disease, which results in various organ pathologies. However, current treatment towards SLE is suboptimal. Erythropoietin (EPO) has been shown to promote SLE recovery, but clinical application can be limited by its haematopoiesis-stimulating effects. EPO-derived helix-B peptide (ARA290) is non-erythrogenic but has been reported to retain the anti-inflammatory and tissue-protective functions of EPO. Therefore, here we investigated the effects and potential mechanisms of ARA290 on SLE...
March 23, 2018: Journal of Cellular and Molecular Medicine
Gregory B Lim
No abstract text is available yet for this article.
March 13, 2018: Nature Reviews. Cardiology
M Jankowski, M Dyszkiewicz-Konwińska, M Magas, M Skorupski, G Gorecki, D Bukowska, P Antosik, M Jeseta, M Bruska, M Nowicki, M Zabel, B Kempisty
Haematopoiesis is one of the most well understood stem-cell associated processes. It is a process in which pluripotent hematopoietic stem cells (HSCs) self-proliferate and differentiate into all types of blood cells. The process takes place in marrow of the flat bones in adults, however its location changes several times through embryonic and foetal development. Given the broad range of blood cells and the major differences in their build and function, together with the fact that their numbers need to be maintained within relatively narrow margins in order to maintain homeostasis despite changing environmental conditions, makes the whole process of haematopoiesis highly regulated and depending on a variety of growth factors...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Kenta Takada, Ryo Amano, Yusuke Nomura, Yoichiro Tanaka, Shigeru Sugiyama, Takashi Nagata, Masato Katahira, Yoshikazu Nakamura, Tomoko Kozu, Taiichi Sakamoto
Since the invention of systematic evolution of ligands by exponential enrichment, many short oligonucleotides (or aptamers) have been reported that can bind to a wide range of target molecules with high affinity and specificity. Previously, we reported an RNA aptamer that shows high affinity to the Runt domain (RD) of the AML1 protein, a transcription factor with roles in haematopoiesis and immune function. From kinetic and thermodynamic studies, it was suggested that the aptamer recognises a large surface area of the RD, using numerous weak interactions...
February 2018: FEBS Open Bio
Tinhinane Fali, Hélène Vallet, Delphine Sauce
Life expectancy is continuously increasing due to major progress in preventing, delaying or curing various pathologies normally encountered in old age. However, both scientific and medical advances are still required to understand underlying cause of the disparate comorbidities occurrence with aging. In one hand, aging profoundly impairs the immune system; it is characterized by many changes in haematopoiesis, adaptive and innate systems, associated with pro-inflammatory environment. In another hand, stressful events (acute or chronic) can also impact the immune system through the secretion of hormones, which are also altered with aging...
May 2018: Experimental Gerontology
Marie Bill, Peter B van Kooten Niekerk, Petter S Woll, Laura Laine Herborg, Anne Stidsholt Roug, Peter Hokland, Line Nederby
The C-type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia-associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking. Here, we have characterized the expression pattern of CLEC12A on the earliest stem- and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC12A expression in the classically defined myeloid progenitors, where on average 39.1% (95% CI [32.5;45.7]) of the common myeloid progenitors (CMPs) expressed CLEC12A, while for granulocyte-macrophage progenitors and megakaryocyte-erythroid progenitors (MEPs), the average percentages were 81...
April 2018: Journal of Cellular and Molecular Medicine
O Akinduro, T S Weber, H Ang, M L R Haltalli, N Ruivo, D Duarte, N M Rashidi, E D Hawkins, K R Duffy, C Lo Celso
Leukaemia progressively invades bone marrow (BM), outcompeting healthy haematopoiesis by mechanisms that are not fully understood. Combining cell number measurements with a short-timescale dual pulse labelling method, we simultaneously determine the proliferation dynamics of primitive haematopoietic compartments and acute myeloid leukaemia (AML). We observe an unchanging proportion of AML cells entering S phase per hour throughout disease progression, with substantial BM egress at high levels of infiltration...
February 6, 2018: Nature Communications
Yuan Kong, Yang Song, Fei-Fei Tang, Hong-Yan Zhao, Yu-Hong Chen, Wei Han, Chen-Hua Yan, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
Prolonged isolated thrombocytopenia (PT) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies and in vitro experiments suggest that mesenchymal stem cells (MSCs) can, not only to support haematopoiesis, but also preferentially support megakaryocytopoiesis in bone marrow (BM). However, little is known about the quantity and function of BM MSCs in PT patients. In a case-control study, we found that BM MSCs from PT patients exhibited significantly reduced proliferative capacities, increased reactive oxygen species and senescence...
March 2018: British Journal of Haematology
Elisa Laurenti, Berthold Göttgens
The development of mature blood cells from haematopoietic stem cells has long served as a model for stem-cell research, with the haematopoietic differentiation tree being widely used as a model for the maintenance of hierarchically organized tissues. Recent results and new technologies have challenged the demarcations between stem and progenitor cell populations, the timing of cell-fate choices and the contribution of stem and multipotent progenitor cells to the maintenance of steady-state blood production...
January 24, 2018: Nature
Toyin Mohammed Salman, Isiaka Abdullateef Alagbonsi, Abdul-Rahuf Aderemi Feyitimi, Peter O Ajayi
ETHNOPHARMACOLOGICAL RELEVANCE: Telfairia occidentalis Hook.f. (TO) is popular in Nigeria for the ethnopharmacological use of its leaves to improve haematological parameters in normal and anaemic subjects. Cytokines are well-known to regulate haematopoiesis. However, their involvement in TO-associated haematopoietic effect is not known and necessitated this study. MATERIALS AND METHODS: Twenty-five (25) male rats were randomly divided into 3 oral treatment groups as follows: Group 1 (control, n=5) received 0...
April 24, 2018: Journal of Ethnopharmacology
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