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Haematopoiesis

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https://www.readbyqxmd.com/read/29147018/enforced-gfi1-expression-impedes-human-and-murine-leukemic-cell-growth
#1
Judith M Hönes, Aniththa Thivakaran, Lacramioara Botezatu, Pradeep Patnana, Symone Vitoriano da Conceição Castro, Yahya S Al-Matary, Judith Schütte, Karen B I Fischer, Lothar Vassen, André Görgens, Ulrich Dührsen, Bernd Giebel, Cyrus Khandanpour
The differentiation of haematopoietic cells is regulated by a plethora of so-called transcription factors (TFs). Mutations in genes encoding TFs or graded reduction in their expression levels can induce the development of various malignant diseases such as acute myeloid leukaemia (AML). Growth Factor Independence 1 (GFI1) is a transcriptional repressor with key roles in haematopoiesis, including regulating self-renewal of haematopoietic stem cells (HSCs) as well as myeloid and lymphoid differentiation. Analysis of AML patients and different AML mouse models with reduced GFI1 gene expression levels revealed a direct link between low GFI1 protein level and accelerated AML development and inferior prognosis...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138493/suppression-of-srcap-chromatin-remodelling-complex-and-restriction-of-lymphoid-lineage-commitment-by-pcid2
#2
Buqing Ye, Benyu Liu, Liuliu Yang, Guanling Huang, Lu Hao, Pengyan Xia, Shuo Wang, Ying Du, Xiwen Qin, Pingping Zhu, Jiayi Wu, Nobuo Sakaguchi, Junyan Zhang, Zusen Fan
Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion. However, how multipotent progenitors (MPP) switch into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP) during this process remains elusive. Here we show that PCI domain-containing protein 2 (Pcid2) is highly expressed in MPPs. Pcid2 deletion in the haematopoietic system causes skewed lymphoid lineage specification. In MPPs, Pcid2 interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CREBBP activator protein (SRCAP) activity and prevents the deposition of histone variant H2A...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29131435/transgenic-characterization-of-two-silkworm-tissue-specific-promoters-in-the-haemocyte-plasmatocyte-cells
#3
K Zhang, C Li, X Weng, J Su, L Shen, G Pan, D Long, A Zhao, H Cui
Haemocytes play crucial roles in insect metabolism, metamorphosis, and innate immunity. As a model of lepidopteran insects, the silkworm is a useful model to study the functions of both haematopoiesis and haemocytes. Tissue-specific promoters are excellent tools for genetic manipulation and are widely used in fundamental biological research. Herein, two haemocyte-specific genes, Integrin β2 and Integrin β3, were confirmed. Promoter activities of Integrin β2 and Integrin β3 were evaluated by genetic manipulation...
November 13, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/29127283/environmental-sensing-by-mature-b-cells-is-controlled-by-the-transcription-factors-pu-1-and-spib
#4
Simon N Willis, Julie Tellier, Yang Liao, Stephanie Trezise, Amanda Light, Kristy O'Donnell, Lee Ann Garrett-Sinha, Wei Shi, David M Tarlinton, Stephen L Nutt
Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29120027/humanised-mouse-models-for-haematopoiesis-and-infectious-diseases
#5
Veronika Lysenko, Donal McHugh, Lena Behrmann, Mary-Aude Rochat, Christian Matthias Wilk, Larisa Kovtonyuk, Jean-Pierre Bourquin, Christian Münz, Markus Gabriel Manz, Roberto Speck, Alexandre Theocharides
"Humanised" mouse models have emerged over past years as powerful tools for investigating human haematopoiesis and immunity. They allowed the identification of key factors for the maintenance and function of normal and leukaemic human haematopoietic stem cells. These findings have been widely used to dissect the pathogenesis of multiple myeloid and lymphoid neoplasms, such as acute myeloid leukaemia and acute lymphoblastic leukaemia. Furthermore, these models can serve as a stepping-stone to clinical trials by testing novel drugs that target leukaemic stem cells...
November 9, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29113189/the-oncogenic-transcription-factor-erg-represses-the-transcription-of-the-tumour-suppressor-gene-pten-in-prostate-cancer-cells
#6
Patricia Adamo, Sean Porazinski, Shavanthi Rajatileka, Samantha Jumbe, Rachel Hagen, Man-Kim Cheung, Ian Wilson, Michael R Ladomery
The oncogene ETS-related gene (ERG) encodes a transcription factor with roles in the regulation of haematopoiesis, angiogenesis, vasculogenesis, inflammation, migration and invasion. The ERG oncogene is activated in >50% of prostate cancer cases, generally through a gene fusion with the androgen-responsive promoter of transmembrane protease serine 2. Phosphatase and tensin homologue (PTEN) is an important tumour suppressor gene that is often inactivated in cancer. ERG overexpression combined with PTEN inactivation or loss is often associated with aggressive prostate cancer...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29104595/structure-and-functions-of-blood-vessels-and-vascular-niches-in-bone
#7
REVIEW
Saravana K Ramasamy
Bone provides nurturing microenvironments for an array of cell types that coordinate important physiological functions of the skeleton, such as energy metabolism, mineral homeostasis, osteogenesis, and haematopoiesis. Endothelial cells form an intricate network of blood vessels that organises and sustains various microenvironments in bone. The recent identification of heterogeneity in the bone vasculature supports the existence of multiple vascular niches within the bone marrow compartment. A unique combination of cells and factors defining a particular microenvironment, supply regulatory signals to mediate a specific function...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29042628/a-dna-contact-map-for-the-mouse-runx1-gene-identifies-novel-haematopoietic-enhancers
#8
Judith Marsman, Amarni Thomas, Motomi Osato, Justin M O'Sullivan, Julia A Horsfield
The transcription factor Runx1 is essential for definitive haematopoiesis, and the RUNX1 gene is frequently translocated or mutated in leukaemia. Runx1 is transcribed from two promoters, P1 and P2, to give rise to different protein isoforms. Although the expression of Runx1 must be tightly regulated for normal blood development, the mechanisms that regulate Runx1 isoform expression during haematopoiesis remain poorly understood. Gene regulatory elements located in non-coding DNA are likely to be important for Runx1 transcription...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29016733/endothelial-to-haematopoietic-transition-contributes-to-pulmonary-arterial-hypertension
#9
Olin D Liang, Eui-Young So, Pamela C Egan, Laura R Goldberg, Jason M Aliotta, Keith Q Wu, Patrycja M Dubielecka, Corey E Ventetuolo, Anthony M Reginato, Peter J Quesenberry, James R Klinger
Aims: The pathogenic mechanisms of pulmonary arterial hypertension (PAH) remain unclear, but involve dysfunctional endothelial cells (ECs), dysregulated immunity and inflammation in the lung. We hypothesize that a developmental process called endothelial to haematopoietic transition (EHT) contributes to the pathogenesis of pulmonary hypertension (PH). We sought to determine the role of EHT in mouse models of PH, to characterize specific cell types involved in this process, and to identify potential therapeutic targets to prevent disease progression...
November 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28973433/lmo2-is-required-for-tal1-dna-binding-activity-and-initiation-of-definitive-haematopoiesis-at-the-haemangioblast-stage
#10
Vesna S Stanulovic, Pierre Cauchy, Salam A Assi, Maarten Hoogenkamp
LMO2 is a bridging factor within a DNA binding complex and is required for definitive haematopoiesis to occur. The developmental stage of the block in haematopoietic specification is not known. We show that Lmo2-/- mouse embryonic stem cells differentiated to Flk-1+ haemangioblasts, but less efficiently to haemogenic endothelium, which only produced primitive haematopoietic progenitors. Genome-wide approaches indicated that LMO2 is required at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements that are important for the establishment of the haematopoietic developmental program...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28965224/effect-of-thrombopoietin-receptor-agonists-on-leukocyte-and-haematopoietic-stem-and-progenitor-cells-in-the-peripheral-blood-of-patients-with-immune-thrombocytopenic-purpura
#11
Gürkan Bal, Depré Fabian, Dzamashvili Maia, Frauke Ringel, Abdulgabar Salama
The thrombopoietin receptor agonists (TPO-RAs), romiplostim and eltrombopag, stimulate megakaryopoiesis and thereby increase platelet counts. Both drugs are increasingly used in the treatment of immune thrombocytopenic purpura (ITP). To assess the effect of TPO-RAs on trilineage haematopoiesis, colony-forming cell (CFC) assays were performed on peripheral blood mononuclear cells of 8 healthy donors and 52 ITP patients. Additionally, we revaluated the regular and complete blood counts (CBCs) performed during romiplostim therapy in 45 patients and the CBCs performed in 9 patients during eltrombopag therapy...
September 30, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28962071/thrombopoietin-mimetics-for-patients-with-myelodysplastic-syndromes
#12
REVIEW
Helga Dodillet, Karl-Anton Kreuzer, Ina Monsef, Nicole Skoetz
BACKGROUND: Myelodysplastic syndrome (MDS) is one of the most frequent haematologic malignancies of the elderly population and characterised by progenitor cell dysplasia with ineffective haematopoiesis and a high rate of transformation to acute myeloid leukaemia (AML). Thrombocytopenia represents a common problem for patients with MDS. ranging from mild to serious bleeding events and death. To manage thrombocytopenia, the current standard treatment includes platelet transfusion, unfortunately leading to a range of side effects...
September 30, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28956197/bone-marrow-sinusoidal-endothelium-damage-and-potential-regeneration-following-cancer-radiotherapy-or-chemotherapy
#13
REVIEW
Mohammadhossein Hassanshahi, Alireza Hassanshahi, Samira Khabbazi, Yu-Wen Su, Cory J Xian
It is very well known that bone marrow (BM) microvasculature may possess a crucial role in the maintenance of homeostasis of BM due to mutual interactions between BM microvascular system and other physiological functions including haematopoiesis and osteogenesis. Chemotherapy and radiotherapy are known as main approaches for cancer treatment and also are known as the main cause of damage to the BM microvascular system. However, despite the importance of BM microvasculature in orchestrating various biological functions, less attention has been drawn to address the underlying mechanisms for the damage and to explore cellular and molecular mechanisms by which the recovery/regeneration of chemotherapy- and/or radiotherapy-induced BM microvascular system damage can occur...
November 2017: Angiogenesis
https://www.readbyqxmd.com/read/28947904/mesenchymal-stem-cells-in-myeloid-malignancies-a-focus-on-immune-escaping-and-therapeutic-implications
#14
REVIEW
Nicola Stefano Fracchiolla, Bruno Fattizzo, Agostino Cortelezzi
The importance of the bone marrow microenvironment forming the so-called niche in physiologic hemopoiesis is largely known, and recent evidences support the presence of stromal alterations from the molecular to the cytoarchitectural level in hematologic malignancies. Various alterations in cell adhesion, metabolism, cytokine signaling, autophagy, and methylation patterns of tumor-derived mesenchymal stem cells have been demonstrated, contributing to the genesis of a leukemic permissive niche. This niche allows both the ineffective haematopoiesis typical of myelodysplastic syndromes and the differentiation arrest, proliferation advantage, and clone selection which is the hallmark of acute myeloid leukemia...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28920953/lifelong-haematopoiesis-is-established-by-hundreds-of-precursors-throughout-mammalian-ontogeny
#15
Miguel Ganuza, Trent Hall, David Finkelstein, Ashley Chabot, Guolian Kang, Shannon McKinney-Freeman
Current dogma asserts that mammalian lifelong blood production is established by a small number of blood progenitors. However, this model is based on assays that require the disruption, transplantation and/or culture of embryonic tissues. Here, we used the sample-to-sample variance of a multicoloured lineage trace reporter to assess the frequency of emerging lifelong blood progenitors while avoiding the disruption, culture or transplantation of embryos. We find that approximately 719 Flk1(+) mesodermal precursors, 633 VE-cadherin(+) endothelial precursors and 545 Vav1(+) nascent blood stem and progenitor cells emerge to establish the haematopoietic system at embryonic days (E)7-E8...
October 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28862380/fetal-bone-marrow-derived-mesenchymal-stem-stromal-cells-enhance-humanization-and-bone-formation-of-bmp7-loaded-scaffolds
#16
Abbas Shafiee, Jeremy G Baldwin, Jatin Patel, Boris M Holzapfel, Nicholas M Fisk, Kiarash Khosrotehrani, Dietmar W Hutmacher
Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis...
September 1, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28861453/data-on-the-effect-of-oral-feeding-of-arachidonic-acid-or-docosahexanoic-acid-on-haematopoiesis-in-mice
#17
Kedar Limbkar, Ankita Dhenge, Dipesh D Jadhav, Hirekodathakallu V Thulasiram, Vaijayanti Kale, Lalita Limaye
Stem cells have peculiar property to self-renew and differentiate. It is important to control their fate in safe and effective ways for their therapeutic use. The mediators of essential polyunsaturated fatty acids (PUFAs) namely Arachidonic acid (AA) and Docosahexanoic acid (DHA) are known to play a role in haematopoiesis via various metabolic pathways [1]. However the direct effect of purified AA or DHA on haematopoiesis has not been well investigated yet. We have reported that oral administration of PUFAs enhanced haematopoiesis in mice [2]...
October 2017: Data in Brief
https://www.readbyqxmd.com/read/28857120/impact-of-genetic-variants-on-haematopoiesis-in-patients-with-thrombocytopenia-absent-radii-tar-syndrome
#18
Georgi Manukjan, Hendrik Bösing, Markus Schmugge, Gabriele Strauß, Harald Schulze
Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions...
August 31, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28846679/microgrooved-surface-topography-enhances-cellular-division-and-proliferation-of-mouse-bone-marrow-derived-mesenchymal-stem-cells
#19
Jitendra Kumar Chaudhary, Pramod C Rath
Mesenchymal stem cells' (MSCs) fate is largely determined by the various topographical features and a range of extracellular matrix (ECM) components present in their niches. Apart from maintaining structural stability, they regulate cell morphology, division, proliferation, migration and differentiation among others. Traditional MSC cultures, which are mainly based on two-dimensional smooth surfaces of culture dishes and plates, do not provide topographical cues similar to in vivo three-dimensional niches, impacting various cellular processes...
2017: PloS One
https://www.readbyqxmd.com/read/28836477/antithrombocytopenic-and-immunomodulatory-potential-of-metabolically-characterized-aqueous-extract-of-carica-papaya-leaves
#20
Varisha Anjum, Poonam Arora, Shahid Husain Ansari, Abul Kalam Najmi, Sayeed Ahmad
CONTEXT: Carica papaya Linn. (Caricaceae) leaf (CPL) juice has long been traditionally used in ethnomedicine for dengue fever. OBJECTIVE: The study examines the effects of standardized CPL aqueous extract (SCPLE) on platelet count, extramedullary haematopoiesis (EMH), and immunomodulation in cyclophosphamide (CP)-induced animal model of thrombocytopenia. MATERIALS AND METHODS: The extract was analyzed for myricetin, caffeic acid, trans-ferulic acid, and kaempferol using HPTLC for standardization followed by UPLC-qTOF/MS fingerprinting for metabolite signature...
December 2017: Pharmaceutical Biology
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