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Haematopoiesis

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https://www.readbyqxmd.com/read/29323290/clonal-analysis-of-lineage-fate-in-native-haematopoiesis
#1
Alejo E Rodriguez-Fraticelli, Samuel L Wolock, Caleb S Weinreb, Riccardo Panero, Sachin H Patel, Maja Jankovic, Jianlong Sun, Raffaele A Calogero, Allon M Klein, Fernando D Camargo
Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate...
January 11, 2018: Nature
https://www.readbyqxmd.com/read/29313948/human-dendritic-cell-subsets-an-update
#2
REVIEW
Matthew Collin, Venetia Bigley
Dendritic cells (DC) are a class of bone marrow derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU...
January 3, 2018: Immunology
https://www.readbyqxmd.com/read/29311715/the-bone-marrow-niche-in-mds-and-mgus-implications-for-aml-and-mm
#3
REVIEW
Irene M Ghobrial, Alexandre Detappe, Kenneth C Anderson, David P Steensma
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...
January 9, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29244714/identification-of-novel-human-nk-cell-progenitor-subsets
#4
Priyanka Sathe, Swee Heng Milon Pang, Rebecca Delconte, Ngaire Elwood, Nicholas D Huntington
Understanding the pathways and regulation of human haematopoiesis, in particular, lymphopoiesis, is vital to manipulation of these processes for therapeutic purposes. However, although haematopoiesis has been extensively characterised in mice, translation of these findings to human biology remains rudimentary. Here, we describe the isolation of three progenitor subsets from human foetal bone marrow that represent differential stages of commitment to the natural killer (NK) cell lineage based on IL-15 responsiveness...
December 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29237808/human-fetal-liver-cultures-support-multiple-cell-lineages-that-can-engraft-immunodeficient-mice
#5
Marina E Fomin, Ashley I Beyer, Marcus O Muench
During prenatal development the liver is composed of multiple cell types with unique properties compared to their adult counterparts. We aimed to establish multilineage cultures of human fetal liver cells that could maintain stem cell and progenitor populations found in the developing liver. An aim of this study was to test if maturation of fetal hepatocytes in short-term cultures supported by epidermal growth factor and oncostatin M can improve their ability to engraft immunodeficient mice. Fetal liver cultures supported a mixture of albumin+ cytokertin-19+ hepatoblasts, hepatocytes, cholangiocytes, CD14++CD32+ liver sinusoidal endothelial cells (LSECs) and CD34+CD133+ haematopoietic stem cells...
December 2017: Open Biology
https://www.readbyqxmd.com/read/29229905/single-cell-rna-sequencing-uncovers-transcriptional-states-and-fate-decisions-in-haematopoiesis
#6
Emmanouil I Athanasiadis, Jan G Botthof, Helena Andres, Lauren Ferreira, Pietro Lio, Ana Cvejic
The success of marker-based approaches for dissecting haematopoiesis in mouse and human is reliant on the presence of well-defined cell surface markers specific for diverse progenitor populations. An inherent problem with this approach is that the presence of specific cell surface markers does not directly reflect the transcriptional state of a cell. Here, we used a marker-free approach to computationally reconstruct the blood lineage tree in zebrafish and order cells along their differentiation trajectory, based on their global transcriptional differences...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29173164/epigenetic-mechanisms-role-in-hematopoietic-stem-cell-lineage-commitment-and-differentiation
#7
Sanjeev Raghuwanshi, Swati Dahariya, Ravinder Kandi, Usha Gutti, Ram Babu Undi, Durga Shankar Sharma, Narasaiah Kovuru, Itishri Sahu, Nagendra Sastry Yarla, Raja Gopal Venakata Saladi, Ravi Kumar Gutti
Major breakthroughs in last several decades have contributed to our knowledge of the genetic regulation in development. Although epigenetics is not a new concept, unfortunately, the role of epigenetics has not come to fruition in large past. But the field of epigenetics has exploded within the past decade. Now, growing evidences show a complex network of epigenetic regulation in development. The epigenetic makeup of a cell, tissue or individual is much more complex than their genetic complement. Epigenetic modifications are more important for normal development by maintaining the gene expression pattern in tissue- and context- specific manner...
November 22, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29171575/a-case-of-hypotriploid-chromosome-in-a-patient-with-acute-lymphoblastic-leukaemia
#8
Bilal Ahmed Khan, Mirza Faris Ali Baig, Nadir Siddiqui
TA 58-61, XXXX, hypotriploid chromosome was detected in the cytogenetics report of a 28 years old female patient, known case of B-cell Acute Lymphoblastic Leukaemia. On admission, the patient had normal physical examination findings and mental status, except history of fever spikes and generalized bone pains. The patient was admitted for induction of chemotherapy. Bone Marrow/Trephine biopsy report showed diffuse infiltration with blast cells with overall cellularity around 80-85% and suppressed normal haematopoiesis...
November 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/29147018/enforced-gfi1-expression-impedes-human-and-murine-leukemic-cell-growth
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
December 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28962071/thrombopoietin-mimetics-for-patients-with-myelodysplastic-syndromes
#20
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
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