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Li-Jie Zhang, Cen Yan, Sarah Schouteden, Xiao-Juan Ma, Dong Zhao, Thorsten Peters, Catherine M Verfaillie, Ying-Mei Feng
RATIONALE: Previously we reported that although the HSPC frequency in bone marrow cells (BMC) was comparable between β2-/- and β2+/+ mice, transplantation of β2-/- BMC into lethally irradiated CD45.1 recipient resulted in more myeloid cell production than β2+/+ BMC. OBJECTIVE: To address if integrin β2 deficiency skews granulocyte/macrophage progenitor (GMP) proliferation. METHODS AND RESULTS: FACS analysis demonstrated that GMP frequency and cell number were higher and megakaryocyte/erythrocyte progenitor (MEP) frequency and cell number were lower in β2-/- mice than β2+/+ mice...
December 11, 2018: Stem Cells
Stefano Gabriele, Marco Canali, Carla Lintas, Roberto Sacco, Maria Cristina Tirindelli, Arianna Ricciardello, Antonio M Persico
Elevated serotonin (5-HT) blood levels, the first biomarker identified in autism research, has been consistently found in 20-30% of patients with Autism Spectrum Disorder (ASD). Hyperserotonemia is mainly due to greater 5-HT uptake into platelets, mediated by the 5-HT transporter (SERT) located at the platelet plasma membrane. The protein complex involved in platelet SERT trafficking and externalization includes integrin β3, the beta subunit of the platelet membrane adhesive GP IIb/IIIa. Integrin β3 is encoded by the ITGB3 gene, previously identified as a QTL for 5-HT blood levels in ASD at SNP rs2317385...
December 7, 2018: Human Molecular Genetics
Mengge Wang, Hongtao Wang, Yuqi Wen, Xiaoyuan Chen, Xin Liu, Jie Gao, Pei Su, Yuanfu Xu, Wen Zhou, Lihong Shi, Jiaxi Zhou
BACKGROUND: Despite considerable progress in the development of methods for hematopoietic differentiation, efficient generation of transplantable hematopoietic stem cells (HSCs) and other genuine functional blood cells from human embryonic stem cells (hESCs) is still unsuccessful. Therefore, a better understanding of the molecular mechanism underlying hematopoietic differentiation of hESCs is highly demanded. METHODS: In this study, by using whole-genome gene profiling, we identified Myeloid Ectopic Viral Integration Site 2 homolog (MEIS2) as a potential regulator of hESC early hematopoietic differentiation...
December 7, 2018: Stem Cell Research & Therapy
Megan S Rost, Ilya Shestopalov, Yang Liu, Andy H Vo, Catherine E Richter, Sylvia M Emly, Francesca G Barrett, David L Stachura, Michael Holinstat, Leonard I Zon, Jordan A Shavit
The NFE2 transcription factor is expressed in multiple hematopoietic lineages with a well-defined role in regulating megakaryocyte biogenesis and platelet production in mammals. Mice deficient in NFE2 develop severe thrombocytopenia with lethality resulting from neonatal hemorrhage. Recent data in mammals reveal potential differences in embryonic and adult thrombopoiesis. Multiple studies in zebrafish have revealed mechanistic insights into hematopoiesis, although thrombopoiesis has been less studied. Rather than platelets, zebrafish possess thrombocytes, which are nucleated cells with similar functional properties...
December 11, 2018: Blood Advances
Amanda Dalby, Jose Ballester-Beltrán, Chiara Lincetto, Annett Mueller, Nicola Foad, Amanda Evans, James Baye, Ernest Turro, Thomas Moreau, Marloes R Tijssen, Cedric Ghevaert
The production of blood cells and their precursors from human pluripotent stem cells (hPSCs) in vitro has the potential to make a significant impact upon healthcare provision. We demonstrate that the forward programming of hPSCs through overexpression of GATA1, FLI1, and TAL1 leads to the production of a population of progenitors that can differentiate into megakaryocyte or erythroblasts. Using "rainbow" lentiviral vectors to quantify individual transgene expression in single cells, we demonstrate that the cell fate decision toward an erythroblast or megakaryocyte is dictated by the level of FLI1 expression and is independent of culture conditions...
November 20, 2018: Stem Cell Reports
Dan-Wei Ren, Wen-Jun Liu
The main physiological function of megakaryocytes is the production of platelets, whose development, maturation and platelet production are a complex regulatory process, and are involved in many factors. In recent years it was found that the lung is also the main site of megakaryocyte-producing platelets in addition to bone marrow. Based on the findings of recent years, this review summarizes the process of megakaryocyte development, maturation and platelet production, with emphasis on the analyzing the regulatory effects of apoptotic factors, miRNA, thrombopoietin and its receptors, interleukins, transcription factors and their corresponding signal pathways on platelet production...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Kent A Riemondy, Monica Ransom, Christopher Alderman, Austin E Gillen, Rui Fu, Jessica Finlay-Schultz, Gregory D Kirkpatrick, Jorge Di Paola, Peter Kabos, Carol A Sartorius, Jay R Hesselberth
Single-cell RNA sequencing (scRNA-seq) methods generate sparse gene expression profiles for thousands of single cells in a single experiment. The information in these profiles is sufficient to classify cell types by distinct expression patterns but the high complexity of scRNA-seq libraries often prevents full characterization of transcriptomes from individual cells. To extract more focused gene expression information from scRNA-seq libraries, we developed a strategy to physically recover the DNA molecules comprising transcriptome subsets, enabling deeper interrogation of the isolated molecules by another round of DNA sequencing...
November 29, 2018: Nucleic Acids Research
J L Mitchell, N J Mutch
Factor (F)XIII is a tranglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA2 B2 has an established function in hemostasis, where its primary substrate is fibrin. A deficiency in FXIII manifests as a severe bleeding diathesis underscoring its importance in this pathway. The cellular form of the enzyme, a homodimer of the A subunits, denoted FXIII-A, has not been studied in as extensive detail. FXIII-A was generally perceived to remain intracellular, due to the lack of a classical signal peptide for its release...
November 29, 2018: Journal of Thrombosis and Haemostasis: JTH
Keiichi Tozawa, Yukako Ono-Uruga, Masaki Yazawa, Taisuke Mori, Mitsuru Murata, Shinichiro Okamoto, Yasuo Ikeda, Yumiko Matsubara
The clinical needs for platelet transfusions are increasing. Donor-dependent platelet transfusions are, however, associated with practical problems, such as the limited supply and the risk of infection. Thus, we developed a manufacturing system for platelets from donor-independent cell source, human adipose-derived mesenchymal stromal/stem cell line (ASCL). ASCL was obtained by upside-down culture flask method. ASCL satisfied the minimal criteria for defining mesenchymal stem cell (MSC) by The International Society for Cellular Therapy...
November 28, 2018: Blood
L J Zeng, C Y Liu, S X Ding, T Zhang, Z H Shao, R Fu
Objective: To explore the expression of SLAMF6 on CD8(+) T cells in patients with severe aplastic anemia (SAA) and its correlation with disease immune status. Methods: By flow cytometry (FCM), SLAMF6 expression level in peripheral blood CD8(+) T cells was detected in 21 patients with SAA and 15 normal controls respectively from February 2017 to April 2018. The correlation between SLAMF6 expression level and hematopoietic functions, including HGB, PLT, the neutrophil granulocyte and reticulocyte absolute value in peripheral blood, hyperplasia degree (percentage of granulocytes, erythrocytes, lymphocytes and megakaryocytes in bone marrow) and perforin, granzyme B, IFN-γ expression level in CD8(+) T cells were evaluated...
November 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Dandan Liu, Jinlan Pan, Chunxiao Wu, Jianying Liang, Jingjing Wang, Suning Chen, Zixing Chen
Isochromosome 20q- (i(20q-)), as a rare reproducible chromosomal anomaly formed on the basis of 20q-, has not been commonly reported. Due to the rarity of this karyotypic anomaly, the bone marrow morphological characteristics of the patients with i(20q-) have not been clarified until now. In this study, the bone marrow cell morphology from MDS patients with isolated i(20q-), isolated 20q-, and normal karyotype was retrospectively compared and statistically analyzed. The results indicated that the isolated i(20q-) was mostly detected in MDS-MLD patients...
November 27, 2018: Annals of Hematology
Shien-Tung Pan, Young-Hyeh Ko, Soo-Yong Tan, Shih-Sung Chuang
BACKGROUND: Primary cutaneous peripheral T-cell lymphomas (PC-PTCLs) are classified into mycosis fungoides (MF) and other rare specific types; and those do not fit into any specific entities are designated as PTCL, not otherwise specified (NOS), an aggressive neoplasm. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive primary intestinal T-cell lymphoma with enteropathy in the non-neoplastic mucosa. We report a rare case of PC-PTCL-NOS with a late relapse solely in the ileum after complete remission...
December 2018: Pathology, Research and Practice
Tadbir K Bariana, Veerle Labarque, Jessica Heremans, Chantal Thys, Mara De Reys, Daniel Greene, Benjamin Jenkins, Luigi Grassi, Denis Seyres, Frances Burden, Deborah Whitehorn, Olga Shamardina, Sofia Papadia, Keith Gomez, Chris Van Geet, Albert Koulman, Willem H Ouwehand, Cedric Ghevaert, Mattia Frontini, Ernest Turro, Kathleen Freson
Sphingolipids are fundamental to membrane trafficking, apoptosis and cell differentiation and proliferation. KDSR or 3-keto-dihydrosphingosine reductase is an essential enzyme for de novo sphingolipid synthesis, and pathogenic mutations in KDSR result in the severe skin disorder erythrokeratodermia variabilis et progressiva-4. Four of the eight reported cases also had thrombocytopenia but the underlying mechanism has remained unexplored. Here we expand upon the phenotypic spectrum of KDSR deficiency with studies in two siblings with novel compound heterozygous variants associated with thrombocytopenia, anemia and minimal skin involvement...
November 22, 2018: Haematologica
Yi-Chien Lu, Chad Sanada, Juliana Xavier-Ferrucio, Lin Wang, Ping-Xia Zhang, H Leighton Grimes, Meenakshi Venkatasubramanian, Kashish Chetal, Bruce Aronow, Nathan Salomonis, Diane S Krause
Megakaryocytic-erythroid progenitors (MEPs) give rise to the cells that produce red blood cells and platelets. Although the mechanisms underlying megakaryocytic (MK) and erythroid (E) maturation have been described, those controlling their specification from MEPs are unknown. Single-cell RNA sequencing of primary human MEPs, common myeloid progenitors (CMPs), megakaryocyte progenitors, and E progenitors revealed a distinct transitional MEP signature. Inferred regulatory transcription factors (TFs) were associated with differential expression of cell cycle regulators...
November 20, 2018: Cell Reports
Xiaoyan Chen, Chunjuan Fang
This study was designed to investigate the effect of salidroside (SAL) on bone marrow haematopoiesis in a mouse model of myelosuppressed anemia. After the mouse model was established by 60Co γ irradiation and cyclophosphamide, pancytopenia and a sharp reduction in bone marrow stromal cells and bone marrow haematopoietic stem cells (lineage-Sca1+c-kit+) were observed. This was greatly alleviated by SAL (25 mg/kg, 50 mg/kg, 100 mg/kg) in a dose-dependent manner (50% effective dose value of 35.7 mg/kg and 61...
November 20, 2018: Journal of Radiation Research
Kai Mu, Jing Zhang, Yan Gu, Hongjuan Li, Yan Han, Na Cheng, Xiaoyu Feng, Guoyu Ding, Rongjun Zhang, Yuqi Zhao, Hongmei Wang
RATIONALE: To explore the curative effect of human umbilical cord-derived mesenchymal stem cell (ucMSC) therapy for patients with liver cirrhosis complicated with immune thrombocytopenia and refractory Henoch-Schonlein purpura (HSP). PATIENT CONCERNS: A 12-year-old boy presented to our hospital with an 11-month history of purpura on the skin of both lower limbs accompanied by thrombocytopenia. The patient had a history of repeated swelling and painful dorsum pedis, followed by skin redness...
November 2018: Medicine (Baltimore)
Anne E Bras, Valerie de Haas, Arthur van Stigt, Mojca Jongen-Lavrencic, H Berna Beverloo, Jeroen G Te Marvelde, C Michel Zwaan, Jacques J M van Dongen, Jeanette H W Leusen, Vincent H J van der Velden
BACKGROUND: While it is known that CD123 is normally strongly expressed on plasmacytoid dendritic cells and completely absent on nucleated red blood cells, detailed information regarding CD123 expression in acute leukemia is scarce and, if available, hard to compare due to different methodologies. METHODS: CD123 expression was evaluated using standardized EuroFlow immunophenotyping in 139 pediatric AML, 316 adult AML, 193 pediatric BCP-ALL, 69 adult BCP-ALL, 101 pediatric T-ALL, and 28 adult T-ALL patients...
November 18, 2018: Cytometry. Part B, Clinical Cytometry
Zhihong Hu, C Bueso Ramos, L Jeffrey Medeiros, Chong Zhao, C Cameron Yin, Shaoying Li, Shimin Hu, Wei Wang, Beenu Thakral, Jie Xu, Srdan Verstovsek, Pei Lin
The concurrent presence of JAK2 V617F, monocytosis and bone marrow fibrosis can be observed in both chronic myelomonocytic leukemia (CMML) and primary myelofibrosis (PMF). It can be challenging to distinguish CMML with JAK2 mutation and fibrosis from other myeloid neoplasms, particularly PMF. To identify key features that may help distinguish these two entities, we retrospectively studied 21 cases diagnosed as "CMML" with JAK2 V617F and bone marrow fibrosis that were identified from a cohort of 610 cases of CMML diagnosed during 2006-2016...
November 15, 2018: Human Pathology
Mengjiao Hu, Pu Liu, Yangyang Liu, Ming Yue, Yi Wang, Shuai Wang, Xiaoyan Chen, Yangfan Zhou, Jiawei Zhou, Xiaosheng Hu, Yuehai Ke, Hu Hu
BACKGROUND: Perpetuation is the final phase of thrombus formation, however it's mechanisms and regulation are poorly understood. OBJECTIVE: To investigate the mechanism of Shp2 in platelet function and thrombosis. METHODS AND RESULTS: We demonstrate that the platelet-expressed SH2 domain-containing protein-tyrosine phosphatase Shp2 is a negative regulator of thrombus stability under high shear stress. In a ferric chloride-induced mesenteric arteriole thrombosis model, megakaryocyte/platelet-specific Shp2-deficient mice showed less thrombi shedding than wild type mice, although their occlusion times were comparable...
November 16, 2018: Journal of Thrombosis and Haemostasis: JTH
Justin Parreno, Velia M Fowler
Tropomodulins (Tmods) are proteins that cap the slow-growing (pointed) ends of actin filaments (F-actin). The basis for our current understanding of Tmod function comes from studies in cells with relatively stable and highly organized F-actin networks, leading to the view that Tmod capping functions principally to preserve F-actin stability. However, not only is Tmod capping dynamic, but it also can play major roles in regulating diverse cellular processes involving F-actin remodeling. Here, we highlight the multifunctional roles of Tmod with a focus on Tmod3...
November 14, 2018: Biophysical Reviews
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