Featured
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Article
| Open AccessVEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation
Acquired mutations of the gene UBA1 occurring in myeloid cells that result in the expression of impaired isoforms of the enzyme E1 have been described in patients with a severe adult onset auto-inflammatory syndrome called VEXAS. Here the authors profile patients with UBA1 mutations presenting with or without VEXAS disease and show VEXAS disease is characterized by inflammasome activation and monocyte dysregulation.
- Olivier Kosmider
- , Céline Possémé
- & Benjamin Terrier
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Article
| Open AccessCebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish
Eosinophils are innate immune cells critical for protection from parasites, but their developmental origin remains under studied. Here they analyze development of eosinophils in zebrafish and find that eosinophilic lineage commitment and differentiation are regulated by the Cebp1-Cebpβ axis.
- Gaofei Li
- , Yicong Sun
- & Yiyue Zhang
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Article
| Open AccessAn IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life
Neutrophils play critical roles in response to infection, and the limit of available neutrophils in neonates and young infants can impact responses to infections, including sepsis. Here the authors identify that the IL-10/DEL-1 axis is involved in emergency granulopoiesis in neonates and suggest a link to sepsis survival in early life.
- Eleni Vergadi
- , Ourania Kolliniati
- & Christos Tsatsanis
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Article
| Open AccessOntogenetically distinct neutrophils differ in function and transcriptional profile in zebrafish
Neutrophil ontogeny in zebrafish may be a continuum or consist of distinct lineages. Here the authors characterise neutrophils derived from rostral blood island and caudal haematopoietic tissue lineages and show differential gene expression and function in steady state and during wound healing.
- Juan P. García-López
- , Alexandre Grimaldi
- & Carmen G. Feijoo
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Article
| Open AccessSingle cell transcriptomics clarifies the basophil differentiation trajectory and identifies pre-basophils upstream of mature basophils
Single cell sequencing can be used to better characterize immune cell progenitors. Here the authors characterize CLEC12Ahi pre-basophils downstream of pre-basophil and mast cell progenitors (pre-BMPs) but upstream of mature basophils and this population includes basophil progenitors (BaPs).
- Kensuke Miyake
- , Junya Ito
- & Hajime Karasuyama
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Article
| Open AccessPrimitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR
The generation of primitive macrophages remains a poorly understood process in humans. Here, the authors identify placental erythro-myeloid progenitors that give rise to foetal macrophages in the early human placenta and demonstrate that epigenetic silencing of the class II transactivator leads to downregulation of HLA-DR in these cells.
- Jake R. Thomas
- , Anna Appios
- & Naomi McGovern
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Article
| Open AccessTesticular macrophages are recruited during a narrow fetal time window and promote organ-specific developmental functions
How testis resident macrophages develop and influence tissue function is not fully understood. Here the authors use mouse lineage tracing methods to document the haematopoietic source, development and recruitment of early testicular macrophages, support of foetal testis differentiation, and interaction with, and promotion of steroidogenesis in, Leydig cells.
- Xiaowei Gu
- , Anna Heinrich
- & Tony DeFalco
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Article
| Open AccessMyeloid cells promote interferon signaling-associated deterioration of the hematopoietic system
Innate and adaptive immune cells function in the homeostasis of haematopoietic stem cells (HSC). Here the authors show that myeloid cells are able to reduce the function of HSCs via interferon signaling through a neutrophil-NK cell dependent process.
- Jacqueline Feyen
- , Zhen Ping
- & Marc H. G. P. Raaijmakers
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Article
| Open AccessA Myb enhancer-guided analysis of basophil and mast cell differentiation
The transcription factor MYB has been shown to regulate haematopoietic stem cells but there could be lineage specific enhancers. Here, using lineage tracing and single cell sequencing the authors characterise a Myb −68 enhancer that regulates the differentiation of mast cells and basophils.
- Takayoshi Matsumura
- , Haruhito Totani
- & Toshio Suda
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Article
| Open AccessTranscription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation
Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation.
- Kim Theilgaard-Mönch
- , Sachin Pundhir
- & Bo T. Porse
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Article
| Open AccessLy6D+Siglec-H+ precursors contribute to conventional dendritic cells via a Zbtb46+Ly6D+ intermediary stage
The ontogeny of conventional and plasmacytoid dendritic cells (DC) and how these two cell types are related is not fully known. Here the authors identify a pool of bone marrow precursor cells expressing Ly6D Siglec-H and Zbtb46 that can differentiate into either cDC or pDC and show that type I IFN can limit cDC and favor pDC output from these precursors.
- Konstantin Lutz
- , Andrea Musumeci
- & Anne B. Krug
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Article
| Open AccessRobust temporal map of human in vitro myelopoiesis using single-cell genomics
The myeloid lineage is central to homeostasis and immunity. The authors provide an atlas of human iPSC-to-myeloid cell differentiation and demonstrate that the in vitro system recapitulates yolk sac differentiation, opening new avenues to human myelopoiesis.
- Clara Alsinet
- , Maria Nascimento Primo
- & Roser Vento-Tormo
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Article
| Open AccessEpigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells
Haematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here the authors demonstrate that differentially accessible regions in aged HSC chromatin are enriched for stress-responsive enhancers and act as an epigenetic hub to augment transcriptional responses of aged HSCs to external stimuli.
- Naoki Itokawa
- , Motohiko Oshima
- & Atsushi Iwama
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Article
| Open AccessEndothelial cell-specific expression of serine/threonine kinase 11 modulates dendritic cell differentiation
In the bone marrow, dendritic cell development is governed by supporting cells, such as endothelial cells. Here authors show that expression of serine/threonine kinase 11 in endothelial cells regulates differentiation of dendritic cell precursors via modulating secretion of stem cell factor.
- Qiang Zhao
- , Young-Min Han
- & Ming-Hui Zou
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Article
| Open AccessMonocyte progenitors give rise to multinucleated giant cells
Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.
- Anne Kathrin Lösslein
- , Florens Lohrmann
- & Philipp Henneke
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Article
| Open AccessEnvironmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice
Type 2 conventional dendritic cells (cDC2) are important immune activators in adults, but their development and functions at the neonatal stage remain unclear. Here the authors show, using fate-mapping and single-cell RNA sequencing, that neonatal cDC2 come from multiple origins, but converge functionally as potent immune activators upon proper stimuli.
- Nikos E. Papaioannou
- , Natallia Salei
- & Barbara U. Schraml
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Article
| Open AccessSingle-cell transcriptome maps of myeloid blood cell lineages in Drosophila
How the Drosophila lymph gland hemocytes develop and are regulated at a single-cell level is unclear. Here, the authors use single-cell RNA sequencing to show heterogeneity of developing hemocytes in the lymph gland and how they react to wasp infestation, and compare hemocytes from two independent origins.
- Bumsik Cho
- , Sang-Ho Yoon
- & Jiwon Shim
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Article
| Open AccessGeneration, localization and functions of macrophages during the development of testis
The developmental origins and functions of testis macrophages remain incompletely characterized. Here, the authors show, using histology, high-dimensional mass cytometry and cell fate-mapping data, that interstitial and peritubular macrophages originate from distinct precursors and contribute distinctly to spermatogenesis.
- Emmi Lokka
- , Laura Lintukorpi
- & Marko Salmi
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Article
| Open AccessDistinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins
Renal macrophages (RMs) can be of bone marrow or embryonic origin, but their abundance, fate and metabolic profiles in physiological and pathogenic settings are still unclear. Here the authors show, by characterizing these two RMs in multiple transgenic mouse lines, that they exhibit distinct dynamics, homeostasis, immune activity, and metabolic properties.
- Fengming Liu
- , Shen Dai
- & Xuebin Qin
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Article
| Open AccessGM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis
Spondyloarthritis pathology is manifested by increased myeloid infiltration of the joints. Here the authors show that in a mouse model of spondyloarthritis, a single dose of a microbial ligand curdlan induces persistent extramedullary myelopoiesis in the spleen and joints, which is driven by GM-CSF and can be amplified by exogenous IL-33.
- Daniel Regan-Komito
- , James W. Swann
- & Thibault Griseri
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Article
| Open AccessDeletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations
The lineage-specific receptor CSF1R controls macrophage development and homeostasis. Here the authors show that deletion of a conserved Csf1r enhancer (FIRE) selectively depletes brain microglia and resident macrophages in the epidermis, kidney, heart and peritoneum of otherwise healthy mice.
- Rocío Rojo
- , Anna Raper
- & Clare Pridans
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Article
| Open AccessFetal-derived macrophages dominate in adult mammary glands
Tissue-resident macrophages are highly specialized phagocytes that serve multiple functions. Here, using high-dimension analyses and fate-mapping experiments, the authors show that fetal liver-derived macrophages dominate the mammary gland in neonatal and adult, and display characteristic phenotypes and functions.
- Norma Jäppinen
- , Inês Félix
- & Marko Salmi
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Article
| Open AccessA miR-150/TET3 pathway regulates the generation of mouse and human non-classical monocyte subset
A decrease in the fraction of non-classical monocytes is a hallmark of chronic myelomonocytic leukaemia. Taking advantage of this abnormal situation, the authors identify a mechanistic link between miR-150 and TET3 as being involved in monocyte subset generation.
- Dorothée Selimoglu-Buet
- , Julie Rivière
- & Eric Solary
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Article
| Open AccessCSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages
Dendritic cells (DC) are important regulators of both innate and adaptive immunity, but how the DC pool is homeostatically maintained in vivo is unclear. Here the authors show that combined deficiency of FLT3 and CSF1R impedes the differentiation of spleen macrophages of embryonic origin that are required for DC homeostasis.
- Gulce Itir Percin
- , Jiri Eitler
- & Claudia Waskow
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Article
| Open AccessTrisomy silencing by XIST normalizes Down syndrome cell pathogenesis demonstrated for hematopoietic defects in vitro
Individuals with Down Syndrome have hematopoietic abnormalities including high risk of leukaemia. Here the authors show that transcriptional silencing of one chromosome 21 by XIST effectively corrects cell function and development to prevent excessive production of megakaryocytes and erythroids, shown during hematopoietic differentiation of human iPSCs in culture.
- Jen-Chieh Chiang
- , Jun Jiang
- & Jeanne B. Lawrence
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Article
| Open AccessA metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways
HLX transcription factor regulates haematopoietic stem and progenitor cell (HSPC) differentiation and is overexpressed in acute myeloid leukemia. Here the authors show that HLX overexpression leads to myeloid differentiation block in zebrafish and human HSPCs by direct regulation of metabolic pathways.
- Indre Piragyte
- , Thomas Clapes
- & Eirini Trompouki
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Article
| Open AccessThe Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow
Hematopoietic stem cells (HSCs) migrate from the fetal liver to the bone marrow (BM) during embryogenesis. Here the authors show that the WAVE2 complex scaffold Hem1 is required for engraftment of HSCs in BM, not through its canonical role regulating actin polymerization, but through c-Abl survival signaling.
- Lijian Shao
- , Jianhui Chang
- & Robert A. Hromas
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Article
| Open AccessBreast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance
Tumors escape the immune system through many mechanisms. Here the authors show that certain tumors inhibit anti-tumor immunity by stopping the production of conventional dendritic cells (cDCs) in the bone marrow, therefore depleting the pool of cDCs available to present antigen to CD8+ T cells.
- Melissa A. Meyer
- , John M. Baer
- & David G. DeNardo
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Article
| Open AccessBone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4
Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.
- Ailing Liu
- , Minhui Chen
- & Lisa Borghesi
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Article
| Open AccessThe tumour microenvironment creates a niche for the self-renewal of tumour-promoting macrophages in colon adenoma
Tissue-resident F4/80hi macrophages can be found both in normal gut as well as in intestinal tumours. Here the authors show that in the colon these macrophages are CCR2-dependent, while in tumours they gain the ability to self-renew, relying on CSF1 and promoting cancer progression.
- Irene Soncin
- , Jianpeng Sheng
- & Christiane Ruedl
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Article
| Open AccessSuppression of SRCAP chromatin remodelling complex and restriction of lymphoid lineage commitment by Pcid2
Haematopoiesis and the generation of lymphoid cell subsets are controlled by delicate genetic programs enforced via epigenetic regulation. Here the authors show that Pcid2 interacts with ZNHIT1, a component of the SRCAP chromatin remodelling complex, to critically modulate the differentiation of multipotent progenitors.
- Buqing Ye
- , Benyu Liu
- & Zusen Fan
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Article
| Open AccessKSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression
RNA-binding proteins (RBPs) regulate RNA activity and are implicated in haematopoietic malignancies, but their role in myeloid cell specification is unclear. Here, the authors show a role for the RBP KSRP in promoting granulocyte fate over monocyte fate through the biogenesis of miR-129 and a decrease in RUNX1.
- Hongmei Zhao
- , Xiaoshuang Wang
- & Jia Yu
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Article
| Open AccessDisruption of the C/EBPα—miR-182 balance impairs granulocytic differentiation
C/EBPα is a critical transcription factor involved in myelopoiesis and its inactivation is associated with acute myeloid leukemia (AML). Here the authors show a negative feedback loop between C/EBPα and miR-182 and identify this miRNA as a marker of high-risk AML.
- Alexander Arthur Wurm
- , Polina Zjablovskaja
- & Gerhard Behre
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Article
| Open AccessThe Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger
Neutrophils are increased in response to injury and infection but how they form from a common granulocyte-macrophage progenitor is unclear. Here, the authors identify a role for the transcriptional repressor ZBTB11 in zebrafish, which is regulated by master myeloid regulators and repressesTP53.
- Maria-Cristina Keightley
- , Duncan P. Carradice
- & Graham J. Lieschke
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Article
| Open AccessRegulation of monocyte cell fate by blood vessels mediated by Notch signalling
Circulating Ly6Clo monocytes are thought to be derived from Ly6Chi subset. Here the authors show that Notch signalling is activated in Ly6Clocells and is required for their differentiation, and that Notch ligands that initiate this signalling are provided by a subset of endothelial cells.
- Jaba Gamrekelashvili
- , Roberto Giagnorio
- & Florian P. Limbourg
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Review Article
| 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 |
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