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Nuclear morphology is shaped by loop-extrusion programs
In neutrophil progenitor cells, stopping the process of loop extrusion by depleting nipped-B-like protein (NIPBL) results in the assembly of polymorphonuclear structures and the activation of a neutrophil-specific gene program.
- Indumathi Patta
- , Maryam Zand
- & Cornelis Murre
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Article
| Open AccessDeciphering cell states and genealogies of human haematopoiesis
An improved, single-cell lineage-tracing system, based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility, is used to define the clonal architecture of haematopoietic stem cells.
- Chen Weng
- , Fulong Yu
- & Vijay G. Sankaran
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Article
| Open AccessModelling post-implantation human development to yolk sac blood emergence
A genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis captures the codevelopment of embryonic tissue and extra-embryonic endoderm and mesoderm niche with early haematopoiesis, with potential for drug testing and disease modelling.
- Joshua Hislop
- , Qi Song
- & Mo R. Ebrahimkhani
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Article |
An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis
Single-cell transcriptomics studies on human and mouse non-small cell lung cancer and conditional knockout mouse models show that IL-4 from bone marrow basophils drives the development of granulocyte-monocyte progenitors to myeloid cells that suppress antitumour immunity.
- Nelson M. LaMarche
- , Samarth Hegde
- & Miriam Merad
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Review Article |
Physiology and diseases of tissue-resident macrophages
This Review addresses the current understanding of the roles of tissue-resident macrophages in physiology and disease, including their development and their functions in tissue remodelling and nutrient recycling.
- Tomi Lazarov
- , Sergio Juarez-Carreño
- & Frederic Geissmann
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Article |
A Prox1 enhancer represses haematopoiesis in the lymphatic vasculature
A transcriptional enhancer element regulates Prox1 expression and lymphatic endothelial cell identity.
- Jan Kazenwadel
- , Parvathy Venugopal
- & Natasha L. Harvey
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Article |
Pre-T cell receptor self-MHC sampling restricts thymocyte dedifferentiation
Aberrant thymocyte developmental programming results when interactions between thymic stroma and pre-T cell receptors occur in the absence of major histocompatibility complex bound to antigen peptide.
- Jonathan S. Duke-Cohan
- , Aoi Akitsu
- & Ellis L. Reinherz
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Article |
Independent origins of fetal liver haematopoietic stem and progenitor cells
In fetal liver, the structure of the differentiated haemapoietic progenitor cell population is established directly from precursor cells, independently of haemapoietic stem cells.
- Tomomasa Yokomizo
- , Takako Ideue
- & Toshio Suda
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Article
| Open AccessDiverse mutational landscapes in human lymphocytes
Sequencing of individual human lymphocyte clones shows that they are highly prone to mutations, with higher burdens in memory cells than in naive cells arising from mutational processes associated with differentiation and tissue residency.
- Heather E. Machado
- , Emily Mitchell
- & Peter J. Campbell
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Article |
Ablation of cDC2 development by triple mutations within the Zeb2 enhancer
The transcription factor NFIL3 acts antagonistically to C/EBP proteins by binding the Zeb2 enhancer to prevent Zeb2 expression and the development of the conventional type 2 dendritic cell lineage.
- Tian-Tian Liu
- , Sunkyung Kim
- & Kenneth M. Murphy
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Article |
Lifelong multilineage contribution by embryonic-born blood progenitors
In situ barcoding and fate mapping in mice reveals that an early wave of progenitor specification, driven by embryonic multipotent progenitor cells, gives rise to adult blood independently of haematopoietic stem cells.
- Sachin H. Patel
- , Constantina Christodoulou
- & Fernando D. Camargo
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Article
| Open AccessClonal dynamics of haematopoiesis across the human lifespan
Haematopoiesis has high clonal diversity up to about 65 years of age, after which diversity drops precipitously owing to positive selection acting on a handful of clones that expand exponentially throughout adulthood.
- Emily Mitchell
- , Michael Spencer Chapman
- & Peter J. Campbell
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Article |
Mapping human haematopoietic stem cells from haemogenic endothelium to birth
The HSC signature RUNX1+HOXA9+MLLT3+MECOM+HLF+SPINK2+ distinguishes haematopoietic stem cells from their endothelial precursors and differentiated progenitors throughout ontogeny
- Vincenzo Calvanese
- , Sandra Capellera-Garcia
- & Hanna K. A. Mikkola
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Article |
Single-cell transcriptomic characterization of a gastrulating human embryo
The single-cell transcriptional profile of a human embryo between 16 and 19 days after fertilization reveals parallels and differences in gastrulation in humans as compared with mouse and non-human primate models.
- Richard C. V. Tyser
- , Elmir Mahammadov
- & Shankar Srinivas
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Article |
Blood and immune development in human fetal bone marrow and Down syndrome
A single-cell atlas of human fetal bone marrow in healthy fetuses and fetuses with Down syndrome provides insight into developmental haematopoiesis in humans and the transcription and functional differences that occur in Down syndrome.
- Laura Jardine
- , Simone Webb
- & Muzlifah Haniffa
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Article |
Lineage tracing of human development through somatic mutations
Whole-genome sequencing of haematopoietic colonies from human fetuses reveals the somatic mutations acquired by individual progenitors, which are used as barcodes to construct a phylogenetic tree of blood development.
- Michael Spencer Chapman
- , Anna Maria Ranzoni
- & Ana Cvejic
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Article |
A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis
A peri-arteriolar niche in the bone marrow for osteogenesis and lymphopoiesis is maintained by mechanical stimulation and is depleted during ageing.
- Bo Shen
- , Alpaslan Tasdogan
- & Sean J. Morrison
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Article |
In situ mapping identifies distinct vascular niches for myelopoiesis
A combination of fluorescent antibodies is used to build visual maps of all myeloid cells in the bone marrow, providing new insight into how the bone marrow microenvironment regulates cell-fate decisions.
- Jizhou Zhang
- , Qingqing Wu
- & Daniel Lucas
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Article |
Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells
A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.
- Erik L. Bao
- , Satish K. Nandakumar
- & Vijay G. Sankaran
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Article |
Deciphering human macrophage development at single-cell resolution
Single-cell RNA sequencing of haematopoietic cells from human embryos at different developmental stages sheds light on the development and specification of macrophages in different tissues.
- Zhilei Bian
- , Yandong Gong
- & Bing Liu
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Article |
Mouse models of neutropenia reveal progenitor-stage-specific defects
Mouse models of severe congenital neutropenia using patient-derived mutations in the GFI1 locus are used to determine the mechanisms by which the disease progresses.
- David E. Muench
- , Andre Olsson
- & H. Leighton Grimes
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Article |
MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment
MLLT3 is identified as a crucial regulator of the self-renewal of human haematopoietic stem cells, and helps to maintain an active chromatin state in haematopoietic stem-cell regulatory genes during culture.
- Vincenzo Calvanese
- , Andrew T. Nguyen
- & Hanna K. A. Mikkola
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Article |
Decoding human fetal liver haematopoiesis
Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.
- Dorin-Mirel Popescu
- , Rachel A. Botting
- & Muzlifah Haniffa
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Letter |
Developmental origin, functional maintenance and genetic rescue of osteoclasts
Multinucleated osteoclasts required for normal bone development and tooth eruption in the mouse originate from embryonic erythro-myeloid progenitors and are maintained after birth by fusion with circulating monocytes.
- Christian E. Jacome-Galarza
- , Gulce I. Percin
- & Frederic Geissmann
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Article |
The bone marrow microenvironment at single-cell resolution
The transcriptional landscape of cell populations of the mouse bone marrow microenvironment, mapped at single-cell resolution, reveals cellular heterogeneity in this niche as well as substantial transcriptional remodelling under stress conditions.
- Anastasia N. Tikhonova
- , Igor Dolgalev
- & Iannis Aifantis
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Article |
Population dynamics of normal human blood inferred from somatic mutations
Analysis of blood from a healthy human show that haematopoietic stem cells increase rapidly in numbers through early life, reaching a stable plateau in adulthood, and contribute to myeloid and B lymphocyte populations throughout life.
- Henry Lee-Six
- , Nina Friesgaard Øbro
- & Peter J. Campbell
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Letter |
Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche
Melanocytes above the haematopoietic niche protect haematopoietic stem cells from ultraviolet-light-induced DNA damage in aquatic vertebrates throughout evolution; this niche moved to the bone marrow during the transition to terrestrial life.
- Friedrich G. Kapp
- , Julie R. Perlin
- & Leonard I. Zon
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Letter |
Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host
Microbial signals are crucial to the development of pre-leukaemic myeloproliferation, which can be induced by disrupting the intestinal barrier or by introducing systemic bacterial stimuli in Tet2-deficient mice.
- Marlies Meisel
- , Reinhard Hinterleitner
- & Bana Jabri
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Letter |
LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis
The HOIL-1 component of the LUBAC ubiquitin ligase complex is required for LUBAC activity, which prevents lethality during embryogenesis by preventing aberrant TNFR1-mediated endothelial cell death and RIPK1-mediated defects in haematopoiesis.
- Nieves Peltzer
- , Maurice Darding
- & Henning Walczak
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Letter |
Regulation of embryonic haematopoietic multipotency by EZH1
The production of haematopoietic stem cells is repressed during early mammalian embryogenesis by an epigenetic mechanism that involves the action of the Polycomb protein EZH1.
- Linda T. Vo
- , Melissa A. Kinney
- & George Q. Daley
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Letter |
Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells
Analysis of transplantation of single haematopoietic stem cells in mice defines stable lineage-restricted fates in long-term self-renewing multipotent stem cells, including a class of multipotent stem cells that exclusively replenishes the megakaryocyte/platelet lineage.
- Joana Carrelha
- , Yiran Meng
- & Sten Eirik W. Jacobsen
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Letter |
Clonal analysis of lineage fate in native haematopoiesis
Transposon tagging to clonally trace progenitors and stem cells provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.
- Alejo E. Rodriguez-Fraticelli
- , Samuel L. Wolock
- & Fernando D. Camargo
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Letter |
A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease
Braf V600E expression in resident macrophage progenitors leads to clonal expansion of ERK-activated microglia, which causes synaptic and neuronal loss in the brain and results in lethal neurodegenerative disease in adult mice.
- Elvira Mass
- , Christian E. Jacome-Galarza
- & Frederic Geissmann
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Letter |
Polylox barcoding reveals haematopoietic stem cell fates realized in vivo
An artificial recombination locus, Polylox, that can generate hundreds of thousands of individual barcodes is used to trace the fates of haematopoietic stem cells in mice.
- Weike Pei
- , Thorsten B. Feyerabend
- & Hans-Reimer Rodewald
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Article |
Haematopoietic stem and progenitor cells from human pluripotent stem cells
Haematopoietic stem and progenitor cell conversion of human pluripotent stem cell-derived haemogenic endothelium.
- Ryohichi Sugimura
- , Deepak Kumar Jha
- & George Q. Daley
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Letter |
The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors
Direct imaging of the lung microcirculation in mice indicates that it is a major site of mature platelet production from megakaryocytes.
- Emma Lefrançais
- , Guadalupe Ortiz-Muñoz
- & Mark R. Looney
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Letter |
Fetal liver endothelium regulates the seeding of tissue-resident macrophages
PLVAP selectively controls the seeding of fetal liver monocyte-derived tissue-resident macrophages, seemingly by interacting with chemotactic and adhesive molecules at the diaphragms of liver sinusoidal endothelium.
- Pia Rantakari
- , Norma Jäppinen
- & Marko Salmi
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Letter |
Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway
Single-cell RNA sequencing of bone marrow innate lymphoid cell (ILC) precursors reveals that PD-1 marks a committed ILC progenitor and that ILC2 development requires Bcl11b and IL-25R expression; activated ILCs can also be depleted by a PD-1 antibody.
- Yong Yu
- , Jason C. H. Tsang
- & Pentao Liu
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Letter |
Single-cell analysis of mixed-lineage states leading to a binary cell fate choice
Stem cells generate progenitors that transition through a series of dynamically unstable states with mixed-lineage gene expression, culminating in the specification of cell-fate.
- Andre Olsson
- , Meenakshi Venkatasubramanian
- & H. Leighton Grimes
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Letter |
Resolving early mesoderm diversification through single-cell expression profiling
Analysis of the transcriptome of more than 1,200 cells from gastrulating mouse embryos using single-cell sequencing, gathering unexpected insights into early mesoderm formation during gastrulation.
- Antonio Scialdone
- , Yosuke Tanaka
- & Berthold Göttgens
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Letter |
Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment
An in vivo imaging-based competitive transplant screen in zebrafish identifies epoxyeicosatrienoic acids as enhancers of haematopoietic stem and progenitor cell (HSPC) engraftment; these derivatives of arachidonic acid also promote zebrafish developmental HSPC specification through a PI(3)K-dependent AP-1 and runx1 transcriptional program and their pro-engraftment effect is conserved in mammals (indicating clinical potential).
- Pulin Li
- , Jamie L. Lahvic
- & Leonard I. Zon
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Letter |
Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
To determine the origin of adult tissue-resident macrophages, a mouse lineage tracing study has revealed that these cells derive from erythro-myeloid progenitors in the yolk sac that are distinct from fetal and adult haematopoietic stem cells.
- Elisa Gomez Perdiguero
- , Kay Klapproth
- & Hans-Reimer Rodewald
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Article |
Clonal dynamics of native haematopoiesis
On the basis of transplantation experiments it is generally believed that a very small number of haematopoietic stem cells maintain multi-lineage haematopoiesis by stably producing a hierarchy of short-lived progenitor cells; here a new transposon-based labelling technique shows that this might not be the case during non-transplant haematopoiesis, but rather that a large number of long-lived progenitors are the main drivers of steady-state haematopoiesis during most of adulthood.
- Jianlong Sun
- , Azucena Ramos
- & Fernando D. Camargo
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Letter |
ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors
Under stress conditions such as acute blood loss or chronic anaemia, glucocorticoids trigger self-renewal of early burst-forming unit–erythroid (BFU–E) progenitors in the spleen, however, the mechanism of glucocorticoid action is not well understood; here the RNA binding protein ZFP36L2 is identified as a transcriptional target of the glucocorticoid receptor in BFU-Es and is shown to be involved in the process of erythroid cell expansion following exposure to glucocorticoids.
- Lingbo Zhang
- , Lina Prak
- & Harvey F. Lodish
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Letter |
Diverse and heritable lineage imprinting of early haematopoietic progenitors
In vivo ‘cellular barcoding’ shows that early haematopoietic progenitors are heterogeneous in the cell types that they produce, and this is partly due to an ‘imprinting’ of fate in progenitors, including for a separate dendritic cell lineage.
- Shalin H. Naik
- , Leïla Perié
- & Ton N. Schumacher
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Letter |
Clonal allelic predetermination of immunoglobulin-κ rearrangement
Immunoglobulin genes are expressed from either the maternal or paternal chromosome; it is now shown that in early haematopoietic stem cells, an individual cell can choose either of the two alleles, but as they develop they become committed to only one.
- Marganit Farago
- , Chaggai Rosenbluh
- & Yehudit Bergman
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Article |
New gene functions in megakaryopoiesis and platelet formation
A meta-analysis of genome-wide association studies in more than 66,000 individuals identifies 68 new genomic loci that reliably associate with platelet count and volume, and reveals new gene functions.
- Christian Gieger
- , Aparna Radhakrishnan
- & Nicole Soranzo
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Research Highlights |
Immune system's bacterial shepherd
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Letter |
TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation
- Mark C. Siracusa
- , Steven A. Saenz
- & David Artis