Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo

Published on Jun 1, 2017in Cell Reports7.815
· DOI :10.1016/j.celrep.2017.05.063
Christoph Hirche2
Estimated H-index: 2
(MHH: Hannover Medical School),
Theresa Frenz10
Estimated H-index: 10
(MHH: Hannover Medical School)
+ 15 AuthorsUlrich Kalinke36
Estimated H-index: 36
(MHH: Hannover Medical School)
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly inv
  • References (47)
  • Citations (13)
📖 Papers frequently viewed together
119 Citations
21 Citations
2 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Simon HaasH-Index: 13
#2Jenny Hansson (EMBL-EBI: European Bioinformatics Institute)H-Index: 12
Last. Marieke A. G. EssersH-Index: 19
view all 20 authors...
119 CitationsSource
#1Aoi JoH-Index: 3
#2Sachiyo MitaniH-Index: 6
Last. Hitoshi IchikawaH-Index: 35
view all 14 authors...
High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML
17 CitationsSource
#1Dagmar WalterH-Index: 4
#2Amelie LierH-Index: 11
Last. Michael D. Milsom (DKFZ: German Cancer Research Center)H-Index: 20
view all 24 authors...
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.
235 CitationsSource
#1Josh CrouseH-Index: 7
#2Ulrich KalinkeH-Index: 36
Last. Annette OxeniusH-Index: 57
view all 3 authors...
Type I interferons (IFNs) have both direct and indirect effects on T cells, and can promote or inhibit their antiviral activity. As reviewed here, the outcome of type I IFN signalling in T cells largely depends on the timing of the signal relative to T cell receptor activation.
149 CitationsSource
#1Hans Heinrich Hoffmann (Rockefeller University)H-Index: 6
#2William M. Schneider (Rockefeller University)H-Index: 10
Last. Catherine M. Rice (Rockefeller University)H-Index: 134
view all 3 authors...
Over half a century has passed since interferons (IFNs) were discovered and shown to inhibit virus infection in cultured cells. Since then, researchers have steadily brought to light the molecular details of IFN signaling, catalogued their pleiotropic effects on cells, and harnessed their therapeutic potential for a variety of maladies. While advances have been plentiful, several fundamental questions have yet to be answered and much complexity remains to be unraveled. We explore the current kno...
145 CitationsSource
#1Katie A. Matatall (Center for Cell and Gene Therapy)H-Index: 3
#2Ching-Chieh Shen (WashU: Washington University in St. Louis)H-Index: 1
Last. Katherine Y. King (Center for Cell and Gene Therapy)H-Index: 12
view all 4 authors...
Interferon gamma (IFNγ) promotes cell division of hematopoietic stem cells (HSCs) without affecting the total HSC number. We postulated that IFNγ stimulates differentiation of HSCs as part of the innate immune response. Here, we report that type II interferon signaling is required, both at baseline and during an animal model of LCMV infection, to maintain normal myeloid development. By separately evaluating myeloid-biased and lymphoid-biased HSC subtypes, we found that myeloid-biased HSCs expres...
29 CitationsSource
#1Tomohiko Sato (UTokyo: University of Tokyo)H-Index: 14
#2Susumu Goyama (UTokyo: University of Tokyo)H-Index: 24
Last. Mineo Kurokawa (UTokyo: University of Tokyo)H-Index: 50
view all 15 authors...
Relapse of chronic myeloid leukemia (CML) is triggered by stem cells with a reconstituting capacity similar to that of hematopoietic stem cells (HSCs) and CML stem cells are a source of resistance in drug therapy with tyrosine kinase inhibitors (TKIs). Ecotropic viral integration site 1 (EVI1), a key transcription factor in HSC regulation, is known to predict poor outcomes in myeloid malignancies, however, incapability of prospective isolation of EVI1-high leukemic cells precludes the functional...
21 CitationsSource
#2Daniel Klimmeck (EMBL-EBI: European Bioinformatics Institute)H-Index: 9
Last. Andreas TrumppH-Index: 56
view all 24 authors...
In this study, we present integrated quantitative proteome, transcriptome, and methylome analyses of hematopoietic stem cells (HSCs) and four multipotent progenitor (MPP) populations. From the characterization of more than 6,000 proteins, 27,000 transcripts, and 15,000 differentially methylated regions (DMRs), we identified coordinated changes associated with early differentiation steps. DMRs show continuous gain or loss of methylation during differentiation, and the overall change in DNA methyl...
211 CitationsSource
#1Franziska DağH-Index: 5
#2Lars Dölken (University of Cambridge)H-Index: 28
Last. Luka Cicin-SainH-Index: 21
view all 18 authors...
Herpesviruses establish a lifelong latent infection posing the risk for virus reactivation and disease. In cytomegalovirus infection, expression of the major immediate early (IE) genes is a critical checkpoint, driving the lytic replication cycle upon primary infection or reactivation from latency. While it is known that type I interferon (IFN) limits lytic CMV replication, its role in latency and reactivation has not been explored. In the model of mouse CMV infection, we show here that IFNβ blo...
33 CitationsSource
#1Eric M. Pietras (UCSF: University of California, San Francisco)H-Index: 22
#2Ranjani Lakshminarasimhan (UCSF: University of California, San Francisco)H-Index: 2
Last. Emmanuelle Passegué (UCSF: University of California, San Francisco)H-Index: 37
view all 7 authors...
Type I interferons (IFN-1s) are antiviral cytokines that suppress blood production while paradoxically inducing hematopoietic stem cell (HSC) proliferation. Here, we clarify the relationship between the proliferative and suppressive effects of IFN-1s on HSC function during acute and chronic IFN-1 exposure. We show that IFN-1–driven HSC proliferation is a transient event resulting from a brief relaxation of quiescence-enforcing mechanisms in response to acute IFN-1 exposure, which occurs exclusiv...
94 CitationsSource
Cited By13
#1Stephan Isringhausen (UZH: University of Zurich)H-Index: 3
#2Larisa V. Kovtonyuk (UZH: University of Zurich)H-Index: 7
Last. Anette Oxenius (ETH Zurich)
view all 11 authors...
Chronic viral infections are associated with hematopoietic suppression and bone marrow (BM) failure, which have been linked to hematopoietic stem cell (HSC) exhaustion. However, how persistent viral infectious challenge and ensuing inflammatory responses target BM tissues and perturb hematopoietic homeostasis remains poorly understood. Here, we combine extensive functional analyses with advanced 3D microscopy to demonstrate that chronic infection with lymphocytic choriomeningitis virus clone 13 ...
#1Rebecca Epperly (St. Jude Children's Research Hospital)H-Index: 1
view all 3 authors...
Chimeric antigen receptor (CAR) T cells targeting CD19 have been successful treating patients with relapsed/refractory B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas. However, relapse after CAR T cell therapy is still a challenge. In addition, preclinical and early clinical studies targeting acute myeloid leukemia (AML) have not been as successful. This can be attributed in part to the presence of an AML microenvironment that has a dampening effect on the antitumor activity of CA...
#1Guodong Tie (UMMS: University of Massachusetts Medical School)H-Index: 9
#2Jinglian Yan (UMMS: University of Massachusetts Medical School)H-Index: 9
Last. Louis M. Messina (UMMS: University of Massachusetts Medical School)H-Index: 51
view all 5 authors...
Hypercholesterolemia accelerates the phenotypes of aging in hematopoietic stem cells (HSCs). As yet, little is known about the underlying mechanism. We found that hypercholesterolemia downregulates Ten eleven translocation 1 (Tet1) in HSCs. The total HSC population was increased, while the long-term (LT) population, side population and reconstitution capacity of HSCs were significantly decreased in Tet1−/− mice. Expression of the Tet1 catalytic domain in HSCs effectively restored the LT populati...
Over the last century, the alarming surge in allergy and autoimmune disease has led to the hypothesis that decreasing exposure to microbes, which has accompanied industrialization and modern life in the Western world, has fundamentally altered the immune response. In its current iteration, the 'hygiene hypothesis' suggests that reduced microbial exposures during early life restricts the production and differentiation of immune cells suited for immune regulation. Although it is now well appreciat...
#1Leonid Olender (BGU: Ben-Gurion University of the Negev)
#2Nir Bujanover (BGU: Ben-Gurion University of the Negev)H-Index: 1
Last. Roi Gazit (BGU: Ben-Gurion University of the Negev)H-Index: 31
view all 5 authors...
Haematopoietic stem cells (HSCs) have the potential for lifetime production of blood and immune cells. The introduction of transgenes into HSCs is important for basic research, as well as for multiple clinical applications, because HSC transplantation is an already established procedure. Recently, a major advancement has been reported in the use of cyclosporine H (CsH), which can significantly enhance the lentivirus (LV) transduction of human haematopoietic stem and progenitor cells (HSPCs). In ...
#1Xinxin Yang (Third Military Medical University)H-Index: 3
#2Degao Chen (Third Military Medical University)
Last. Bo Zhu (Third Military Medical University)H-Index: 22
view all 4 authors...
Extramedullary hematopoiesis (EMH) is the expansion and differentiation of hematopoietic stem and progenitor cells outside of the bone marrow. In postnatal life, as a compensatory mechanism for ineffective hematopoiesis of the bone marrow, pathological EMH is triggered by hematopoietic disorders, insufficient hematopoietic compensation, and other pathological stress conditions, such as infection, advanced tumors, anemia, and metabolic stress. Pathological EMH has been reported in many organs, an...
#1Barbara MaurerH-Index: 4
#2Sebastian KollmannH-Index: 2
Last. Sexl
view all 5 authors...
The transcription factors STAT5A and STAT5B have essential roles in survival and proliferation of hematopoietic cells—which have been considered largely redundant. Mutations of upstream kinases, copy number gains, or activating mutations in STAT5A, or more frequently in STAT5B, cause altered hematopoiesis and cancer. Interfering with their activity by pharmacological intervention is an up-and-coming therapeutic avenue. Precision medicine requests detailed knowledge of STAT5A’s and STAT5B’s indiv...
#1Dorian Forte (University of Cambridge)H-Index: 6
#2Daniela S. Krause (Goethe University Frankfurt)H-Index: 1
Last. Simón Méndez-Ferrer (University of Cambridge)H-Index: 23
view all 5 authors...
In this review article, we present recent updates on the hematologic tumor microenvironment following the 3rd Scientific Workshop on the Haematological Tumour Microenvironment and its Therapeutic Targeting organized by the European School of Hematology, which took place at the Francis Crick Institute in London in February 2019. This review article is focused on recent scientific advances highlighted in the invited presentations at the meeting, which encompassed the normal and malignant niches su...
3 CitationsSource
#1Christelle Langevin (Université Paris-Saclay)H-Index: 16
#2Pierre Boudinot (Université Paris-Saclay)H-Index: 39
Last. Bertrand Collet (Université Paris-Saclay)H-Index: 32
view all 3 authors...
The overarching structure of the type I interferon (IFN) system is conserved across vertebrates. However, the variable numbers of whole genome duplication events during fish evolution offer opportunities for the expansion, diversification, and new functionalization of the genes that are involved in antiviral immunity. In this review, we examine how fish models provide new insights about the implication of virus-driven inflammation in immunity and hematopoiesis. Mechanisms that have been discover...
1 CitationsSource
#1Li‐Jie Zhang (Capital Medical University)H-Index: 1
#2Cen Yan (Capital Medical University)H-Index: 1
Last. Yuanbo Feng (Katholieke Universiteit Leuven)H-Index: 20
view all 8 authors...
1 CitationsSource