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| Open AccessResilient anatomy and local plasticity of naive and stress haematopoiesis
This study develops a method for spatially resolving multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice and uncovers heterogeneous haematopoietic stress responses in different bones.
- Qingqing Wu
- , Jizhou Zhang
- & Daniel Lucas
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Article
| Open AccessEpitope editing enables targeted immunotherapy of acute myeloid leukaemia
Epitope engineering of donor haematopoietic stem/progenitor cells endows haematopoietic lineages with selective resistance to CAR T cells or monoclonal antibodies, without affecting protein function or regulation, enabling the targeting of genes that are essential for leukaemia survival and reducing the risk of tumour immune escape.
- Gabriele Casirati
- , Andrea Cosentino
- & Pietro Genovese
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Article
| Open AccessUltraviolet radiation shapes dendritic cell leukaemia transformation in the skin
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) arises from clonal (premalignant) haematopoietic precursors in the bone marrow, and BPDCN skin tumours first develop at sun-exposed anatomical sites and are distinguished by clonally expanded mutations induced by ultraviolet radiation.
- Gabriel K. Griffin
- , Christopher A. G. Booth
- & Andrew A. Lane
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Article |
Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis
Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.
- Joshua S. Weinstock
- , Jayakrishnan Gopakumar
- & Siddhartha Jaiswal
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Article |
Chemically defined cytokine-free expansion of human haematopoietic stem cells
A culture system allows the long-term expansion of human haematopoietic stem cells (HSCs) in vivo without the use of recombinant cytokines or albumin, with potential applications for clinical therapies involving HSCs.
- Masatoshi Sakurai
- , Kantaro Ishitsuka
- & Satoshi Yamazaki
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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 |
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 |
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 |
Aged skeletal stem cells generate an inflammatory degenerative niche
An analysis of skeletal stem cells in mice reveals that bone ageing occurs at the level of local niches affecting skeletal and haematopoietic lineage output, which may influence systemic aspects of multi-organ physiological ageing.
- Thomas H. Ambrosi
- , Owen Marecic
- & Charles K. F. Chan
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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 |
Chaperone-mediated autophagy sustains haematopoietic stem-cell function
Haematopoietic stem cells show progressive functional decline with age that can be reversed by stimulation of chaperone-mediated autophagy in old mice and aged humans.
- Shuxian Dong
- , Qian Wang
- & Ana Maria Cuervo
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Article |
Nociceptive nerves regulate haematopoietic stem cell mobilization
Stimulation of pain-sensing neurons, which can be achieved in mice by the ingestion of capsaicin, promotes the migration of haematopoietic stem cells from the bone marrow into the blood.
- Xin Gao
- , Dachuan Zhang
- & Paul S. Frenette
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Article |
Inherited causes of clonal haematopoiesis in 97,691 whole genomes
Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.
- Alexander G. Bick
- , Joshua S. Weinstock
- & Pradeep Natarajan
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Article |
Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis
Using single-cell lineage tracing, the authors identify TCF15 as a novel regulator of haematopoietic stem cell quiescence and self-renewal.
- Alejo E. Rodriguez-Fraticelli
- , Caleb Weinreb
- & Fernando D. Camargo
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Article |
Single-molecule imaging of transcription dynamics in somatic stem cells
Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.
- Justin C. Wheat
- , Yehonatan Sella
- & Ulrich Steidl
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Article |
DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis
The catalytic subunit of DNA-PK autophosphorylates and contributes to ribosome biogenesis and haematopoiesis by binding to the U3 small nucleolar RNA.
- Zhengping Shao
- , Ryan A. Flynn
- & Eliezer Calo
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Article |
Live-animal imaging of native haematopoietic stem and progenitor cells
A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.
- Constantina Christodoulou
- , Joel A. Spencer
- & Fernando D. Camargo
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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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Letter |
Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells
The cellular degradative machinery can be asymmetrically inherited upon haematopoietic-stem-cell division, which predicts the future metabolic and translational activation of their daughter cells.
- Dirk Loeffler
- , Arne Wehling
- & Timm Schroeder
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Letter |
Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation
An albumin-free culture system for the long-term ex vivo expansion of mouse haematopoietic stem cells produces 236- to 899-fold expansion, and generates cultures that robustly engraft in recipient mice without toxic pre-conditioning.
- Adam C. Wilkinson
- , Reiko Ishida
- & Satoshi Yamazaki
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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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Letter |
Complex mammalian-like haematopoietic system found in a colonial chordate
The identification of a complex haematopoietic system in a colonial tunicate sheds light on the evolution of the mammalian blood system.
- Benyamin Rosental
- , Mark Kowarsky
- & Ayelet Voskoboynik
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Letter |
VCAM-1+ macrophages guide the homing of HSPCs to a vascular niche
In zebrafish embryogenesis, nascent haematopoietic stem and progenitor cells (HSPCs), homing to a vascular niche for retention, are ushered by patrolling and guiding macrophages through integrin-mediated cell-cell recognition.
- Dantong Li
- , Wenzhi Xue
- & Weijun Pan
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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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Review Article |
From haematopoietic stem cells to complex differentiation landscapes
- Elisa Laurenti
- & Berthold Göttgens
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Letter |
A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies
A blood enhancer cluster forms a highly combinatorial system that allows precise control of Myc expression across normal and leukaemic haematopoietic stem-cell hierarchies.
- Carsten Bahr
- , Lisa von Paleske
- & François Spitz
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Article |
Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells
Endogenous and alcohol-derived acetaldehyde causes a specific pattern of DNA damage in haemopoietic stem cells; the effects are mitigated by detoxification, specific DNA repair mechanisms and a p53 response.
- Juan I. Garaycoechea
- , Gerry P. Crossan
- & Ketan J. Patel
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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 |
m6A modulates haematopoietic stem and progenitor cell specification
N6-methyladenosine modification of mRNA determines cell fate decisions during the specification of the first haematopoietic stem cells in zebrafish.
- Chunxia Zhang
- , Yusheng Chen
- & Feng Liu
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Article |
Ascorbate regulates haematopoietic stem cell function and leukaemogenesis
Ascorbate depletion in mice increased haematopoietic stem-cell frequency and promoted leukaemogenesis, partly by reducing the function of the Tet2 tumour suppressor enzyme.
- Michalis Agathocleous
- , Corbin E. Meacham
- & Sean J. Morrison
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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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Article |
Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis
During emergency myelopoiesis in mice, clusters of self-renewing granulocyte/macrophage progenitors (GMP) are transiently formed in the bone marrow cavity to produce a burst of myeloid cells; in leukaemia, GMP clusters persist and constantly generate myeloid leukaemia cells.
- Aurélie Hérault
- , Mikhail Binnewies
- & Emmanuelle Passegué
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Article |
Autophagy maintains the metabolism and function of young and old stem cells
Loss of autophagy increases the accumulation of mitochondria and the respiration status of haematopoietic stem cells, which perturbs their self-renewal and regeneration activities, and promotes cellular aging.
- Theodore T. Ho
- , Matthew R. Warr
- & Emmanuelle Passegué
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Article |
CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells
These preclinical studies outline a CRISPR-based methodology for correcting β-globin gene mutations in haematopoietic stem cells to advance the development of next-generation therapies for β-haemoglobinopathies.
- Daniel P. Dever
- , Rasmus O. Bak
- & Matthew H. Porteus
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Letter |
Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment
Mutations in the protein tyrosine phosphatase SHP2 affect cells in the bone marrow environment, which leads to aberrant activation of resident haematopoietic stem cells and thereby contributes to the development of leukaemia.
- Lei Dong
- , Wen-Mei Yu
- & Cheng-Kui Qu
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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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Article |
Tracing haematopoietic stem cell formation at single-cell resolution
Successful identification of mouse embryonic pre-haematopoietic stem cells at single-cell resolution.
- Fan Zhou
- , Xianlong Li
- & Bing Liu
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Letter |
Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells
The RNA-binding protein Musashi-2 increases the self-renewing abilities of human haematopoietic stem cells, which have the potential to be used for regenerative therapies.
- Stefan Rentas
- , Nicholas T. Holzapfel
- & Kristin J. Hope
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Article |
Distinct bone marrow blood vessels differentially regulate haematopoiesis
Bone marrow endothelial cells have dual roles in the regulation of haematopoietic stem cell maintenance and in the trafficking of blood cells between the bone marrow and the blood circulatory system; this study shows that these different functions are regulated by distinct types of endothelial blood vessels with different permeability properties, affecting the metabolic state of their neighbouring stem cells.
- Tomer Itkin
- , Shiri Gur-Cohen
- & Tsvee Lapidot
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Letter |
Age-dependent modulation of vascular niches for haematopoietic stem cells
Notch signalling in endothelial cells of the bone induces change in the capillaries and mesenchymal stem cells of the environment to support haematopoietic stem cell amplification.
- Anjali P. Kusumbe
- , Saravana K. Ramasamy
- & Ralf H. Adams
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Letter |
Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche
Until recently, complex multi-parameters were required for the isolation and identification of haematopoietic stem cells, complicating study of their biology in situ; here the authors have found that expression of a single gene, Hoxb5, defines haematopoietic stem cells with long-term reconstitution capacity, and that these cells are mainly found in direct contact with endothelial cells.
- James Y. Chen
- , Masanori Miyanishi
- & Irving L. Weissman
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Letter |
Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential
The role of mitochondria in haematopoietic stem-cell maintenance has not been examined in detail; here mitofusin 2, which modulates mitochondrial fusion and tethering of endoplasmic reticulum to the mitochondria, is shown to be necessary for the maintenance of haematopoietic stem cells with extensive lymphoid potential.
- Larry L. Luchsinger
- , Mariana Justino de Almeida
- & Hans-Willem Snoeck
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Article |
A perisinusoidal niche for extramedullary haematopoiesis in the spleen
Haematopoietic stem cells normally reside in a bone marrow niche but they are recruited to the spleen after physiological stresses; here, endothelial cells and stromal cells around sinusoidal blood vessels of the spleen are shown to secrete key niche factors to support this process.
- Christopher N. Inra
- , Bo O. Zhou
- & Sean J. Morrison
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Letter |
Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal
α-catulin is identified as a marker to locate functional haematopoiteic stem cells in deep imaging experiments of bone marrow, showing that α-catulin–GFP+c-kit+ cells commonly reside in perisinusoidal niches throughout the bone marrow.
- Melih Acar
- , Kiranmai S. Kocherlakota
- & Sean J. Morrison
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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 |
Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system.
- Dagmar Walter
- , Amelie Lier
- & Michael D. Milsom
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Letter |
Fundamental properties of unperturbed haematopoiesis from stem cells in vivo
Inducible genetic labelling of haematopoietic stem cells (HSCs) and linked mathematical modelling show that at least 30% of all HSCs are productive, and that adult haematopoiesis is largely sustained by ‘short-term’ downstream stem cells that operate near self-renewal in the steady state; HSC fate mapping provides a quantitative model for better understanding of HSC functions in health and disease.
- Katrin Busch
- , Kay Klapproth
- & Hans-Reimer Rodewald