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| Open AccessRecommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population expanded in cancer and other chronic inflammatory conditions. Here the authors identify the challenges and propose a set of minimal reporting guidelines for mouse and human MDSC.
- Vincenzo Bronte
- , Sven Brandau
- & Dmitry I. Gabrilovich
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Article
| Open AccessDefects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg2+ homeostasis and cytoskeletal architecture
Although Mg2+is vital for platelet activation and aggregation, its regulation in these cells is still largely unknown. Here, the authors show that TRPM7, a cation channel and a protein kinase, regulates thrombopoiesis and platelet size by affecting the cytoskeleton of these cells in mice and humans.
- Simon Stritt
- , Paquita Nurden
- & Attila Braun
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Article
| Open AccessSingle-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells
With age, haematopoietic stem cells (HSCs) produce more myeloid than lymphoid cells, affecting adaptive immunity. By combining HSC single cell transcriptomics with functional studies, Grover et al. find that platelet production is also increased in old murine HSCs and show that the FOG-1 transcription factor contributes to the age-dependent platelet bias.
- Amit Grover
- , Alejandra Sanjuan-Pla
- & Claus Nerlov
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Article
| Open AccessAcetylation of C/EBPα inhibits its granulopoietic function
C/EBPα is an essential transcription factor for myeloid lineage commitment. Here, the authors show that acetylation of C/EBPα at K298 and K302, mediated at least in part by GCN5, impairs C/EBPα DNA binding ability and modulates C/EBPα transcriptional activity.
- Deepak Bararia
- , Hui Si Kwok
- & Daniel G. Tenen
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Article
| Open AccessSTAT5-regulated microRNA-193b controls haematopoietic stem and progenitor cell expansion by modulating cytokine receptor signalling
MicroRNAs regulate haematopoietic stem cell (HSC) development to ensure the correct generation of blood cells. Haetscher et al. show in mice that miR-193b controls the life-long self-renewal ability of HSCs via AKT and STAT5 pathways, with loss of miR-193b accelerating HSC expansion and reducing differentiation.
- Nadine Haetscher
- , Yonatan Feuermann
- & Michael A. Rieger
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Article
| Open AccessControl of developmentally primed erythroid genes by combinatorial co-repressor actions
Conserved sets of transcription factors (TFs) regulate hematopoiesis. Here, Stadhouders et al. show that IRF2BP2 is a component of the LDB1 TF complex and together with its co-repressor ETO2, enhances transcriptional repression, which plays a crucial role at the erythroid progenitor stage.
- Ralph Stadhouders
- , Alba Cico
- & Eric Soler
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Article
| Open AccessReplication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality
What causes hematopoietic stem cell loss of functionality? Here, Alvarez et al. show that loss of origin licensing factor MCM3 induces replicative stress (RS), causing aberrant erythrocyte maturation, but mice strains with higher tolerance to RS can overcome this defect.
- Silvia Alvarez
- , Marcos Díaz
- & Juan Méndez
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Article
| Open AccessA PI3K p110β–Rac signalling loop mediates Pten-loss-induced perturbation of haematopoiesis and leukaemogenesis
The tumor suppressor PTEN antagonizes the PI3K signalling pathway and is frequently inactivated in haematological malignancies. Here, the authors unravel the main contribution of the PI3K isoform p110ß to leukemic transformation driven by PTEN-loss.
- Haluk Yuzugullu
- , Lukas Baitsch
- & Jean J. Zhao
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Article
| Open AccessDesialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia
Immune thrombocytopenia (ITP) is caused by autoantibody-mediated platelet clearance, but refractoriness to current immunomodulatory therapies is common. Here the authors show that desialylated platelets can be cleared via hepatic Ashwell–Morell receptor, a process that can be attenuated by sialidase inhibitors, suggesting a new therapy for ITP.
- June Li
- , Dianne E. van der Wal
- & Heyu Ni
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Article
| Open AccessPlatelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex
During early platelet spreading a novel F-actin structure forms, called the actin nodule. Here Poulter et al.demonstrate that actin nodule formation depends on WASp and the Arp2/3 complex, and using super-resolution microscopy they show that nodules bear a structural resemblance to podosomes.
- Natalie S. Poulter
- , Alice Y. Pollitt
- & Steven G. Thomas
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Article |
Mir-17–92 regulates bone marrow homing of plasma cells and production of immunoglobulin G2c
After activation and selection, plasma cells home to the bone marrow where they persist and continue to make antibodies. Here the authors show that the mir-17–92cluster coordinates the process by regulating the homing receptor S1PR1 and the transcription factor IKAROS that controls IgG2c production.
- Shengli Xu
- , Xijun Ou
- & Kong-Peng Lam
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The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function
The lipid kinase PI3KC2α is essential for embryogenesis, yet its role in adult homeostasis is unknown. Here, the authors show that PI3KC2α regulates the structure of the internal membrane reserves of murine megakaryocytes and platelets, affecting the platelets’ adhesiveness and prothrombotic function.
- Jessica K. Mountford
- , Claire Petitjean
- & Shaun P. Jackson
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Primitive macrophages control HSPC mobilization and definitive haematopoiesis
Haematopoietic stem/progenitor cells (HSPCs) transform from aortic endothelium into migratory cells that move through stroma and enter circulation to colonize haematopoietic tissues. Here the authors show that HSPCs' passage is facilitated by primitive macrophages that secrete extracellular matrix-degrading enzymes.
- Jana Travnickova
- , Vanessa Tran Chau
- & Karima Kissa
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Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development
Regulation of CD4 and CD8 expression during thymic development is a classical model to study control of lineage determination. Here the authors show that Brd1 epigenetically marks CD8 enhancer for activation by mediating H3K14 acetylation, which is necessary for establishing the CD8 T-cell lineage.
- Yuta Mishima
- , Changshan Wang
- & Atsushi Iwama
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IRF8 inhibits C/EBPα activity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils
The mechanisms mediating lineage restriction in haematopoietic cell differentiation are not well understood. Here the authors show when and how the transcription factor IRF8 inhibits neutrophil differentiation during the lineage selection of monocytes and dendritic cells.
- Daisuke Kurotaki
- , Michio Yamamoto
- & Tomohiko Tamura
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Article |
Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators
The haemogenic endothelium gives rise to haematopoietic cells including haematopoietic stem cells. Here, the authors show that the transduction of two combinations of transcription factors into human pluripotent stem cells convert these into haemogenic endothelial cells with distinct lineage potentials.
- Irina Elcheva
- , Vera Brok-Volchanskaya
- & Igor Slukvin
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Article
| Open AccessPADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation
Peptidylarginine deiminase 4 (PADI4) is a transcriptional co-regulator that converts arginine residues at histone tails to citrulline. The authors show that PADI4 interacts with the central haematopoietic transcription factor TAL1 to regulate gene expression in an erythroleukemia cell line.
- Stephan Kolodziej
- , Olga N. Kuvardina
- & Jörn Lausen
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Functional and molecular features of the calmodulin-interacting protein IQCG required for haematopoiesis in zebrafish
NUP98–IQCG is a fusion protein found in acute leukaemia that functions as a regulator of transcriptional expression. Here, Chen et al. investigate IQCG-mediated calcium signalling in haematopoiesis, and propose a model where IQCG can store calmodulin, which once released, activates CaM-dependent kinase IV.
- Li-Ting Chen
- , Wen-Xue Liang
- & Sai-Juan Chen
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Article |
Platelet production proceeds independently of the intrinsic and extrinsic apoptosis pathways
Platelet production has been suggested to occur by apoptosis of megakaryocytes, but mitochondrially mediated apoptosis is known to be dispensable. Here, the authors show that death receptor-mediated apoptosis in mouse megakaryocytes is also not required for platelet biogenesis.
- Emma C. Josefsson
- , Deborah L. Burnett
- & Benjamin T. Kile
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Article |
A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish
The telomerase reverse transcriptase promotes the development of haematopoietic cells in zebrafish independent of its telomere-lengthening activity. Here Alcaraz-Pérez et al.show that the telomerase RNA component regulates cell fate during zebrafish myelopoiesis also in a non-canonical manner.
- Francisca Alcaraz-Pérez
- , Jesús García-Castillo
- & María L. Cayuela
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Article
| Open AccessmiRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1
Several microRNAs have been implicated in the differentiation of immune cells. Here the authors analyse the global microRNA expression profiles of mouse haematopoietic stem cells and different stages of dendritic cell development and identify Notch1 as a target of miR-30b in regulatory dendritic cells.
- Xiaoping Su
- , Cheng Qian
- & Xuetao Cao
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Article |
Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis
The kidney and liver are the sources of erythropoietin required for definitive erythropoiesis, the second wave of erythrocyte formation for later embryonic and adult usage. Here the authors show that mouse embryonic neuroepithelial cells produce erythropoietin during mid-gestation, when primitive erythropoiesis occurs in the yolk sac.
- Norio Suzuki
- , Ikuo Hirano
- & Masayuki Yamamoto
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Article |
Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway
Sepsis in patients is often accompanied by thrombocytopenia, but the exact role of platelets in the pathogenesis of septicaemia has not been elucidated. Here, Xiang et al. present evidence that platelets may act as anti-inflammatory cells and protect from septic shock.
- Binggang Xiang
- , Guoying Zhang
- & Zhenyu Li
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Article |
Haemogenic endocardium contributes to transient definitive haematopoiesis
Cardiac and endocardial/endothelial cells arise from progenitor cells expressing multiple haematopoietic transcription factors. Nakano and colleagues find that Nkx2–5-positive endocardial cells serve as a de novosource for definitive haematopoietic progenitors during mammalian embryogenesis.
- Haruko Nakano
- , Xiaoqian Liu
- & Atsushi Nakano
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Article |
Microtubule and cortical forces determine platelet size during vascular platelet production
Platelets are formed from megakaryocytes but the exact mechanisms are unknown. Thonet al.describe circular preplatelets and barbell shaped proplatelets in human blood and demonstrate, with the aid of a mathematical model, a role for microtubule-based forces in regulating final platelet size.
- Jonathan N Thon
- , Hannah Macleod
- & Joseph E. Italiano Jr
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Article
| Open AccessThe Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice
Post-translational modifications are important in regulating protein function and turnover, and Ufm1 is part of a recently identified protein modification system. In this study, the authors show that Uba5, a component of the Ufm1 system, is important for regulating haematopoiesis and the differentiation of erythroid cells.
- Kanako Tatsumi
- , Harumi Yamamoto-Mukai
- & Masaaki Komatsu