Journal: Blood

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American Society of Hematology

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ISSN

0006-4971
1528-0020

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Publications 1 - 10 of 79
  • Impact of Recombinant Factor VIII and Platelet Interaction on Platelet Functionality and Hemophilia a Treatment
    Item type: Other Conference Item
    Strebel, Anja; Pennacchio, Fabrizio; Lickert, Sebastian; et al. (2023)
    Blood
  • Binding to Platelets Differs Among Recombinant Factor VIII Products in Vitro
    Item type: Other Conference Item
    Lickert, Sebastian; Pennacchio, Fabrizio; Vogel, Viola (2022)
    Blood
  • Identification of factors promoting ex vivo maintenance of mouse hematopoietic stem cells by long-term single-cell quantification
    Item type: Journal Article
    Kokkaliaris, Konstantinos D.; Drew, Erin; Endele, Max; et al. (2016)
    Blood
  • JAK2-V617F and interferon-α induce megakaryocyte-biased stem cells characterized by decreased long-term functionality
    Item type: Journal Article
    Rao, Tata Nageswara; Hansen, Nils; Stetka, Jan; et al. (2021)
    Blood
    We studied a subset of hematopoietic stem cells (HSCs) that are defined by elevated expression of CD41 (CD41hi) and showed bias for differentiation toward megakaryocytes (Mks). Mouse models of myeloproliferative neoplasms (MPNs) expressing JAK2-V617F (VF) displayed increased frequencies and percentages of the CD41hi vs CD41lo HSCs compared with wild-type controls. An increase in CD41hi HSCs that correlated with JAK2-V617F mutant allele burden was also found in bone marrow from patients with MPN. CD41hi HSCs produced a higher number of Mk-colonies of HSCs in single-cell cultures in vitro, but showed reduced long-term reconstitution potential compared with CD41lo HSCs in competitive transplantations in vivo. RNA expression profiling showed an upregulated cell cycle, Myc, and oxidative phosphorylation gene signatures in CD41hi HSCs, whereas CD41lo HSCs showed higher gene expression of interferon and the JAK/STAT and TNFα/NFκB signaling pathways. Higher cell cycle activity and elevated levels of reactive oxygen species were confirmed in CD41hi HSCs by flow cytometry. Expression of Epcr, a marker for quiescent HSCs inversely correlated with expression of CD41 in mice, but did not show such reciprocal expression pattern in patients with MPN. Treatment with interferon-α further increased the frequency and percentage of CD41hi HSCs and reduced the number of JAK2-V617F+ HSCs in mice and patients with MPN. The shift toward the CD41hi subset of HSCs by interferon-α provides a possible mechanism of how interferon-α preferentially targets the JAK2 mutant clone. © 2021 American Society of Hematology
  • Asymmetric organelle inheritance predicts human blood stem cell fate
    Item type: Journal Article
    Loeffler, Dirk; Schneiter, Florin; Wang, Weijia; et al. (2022)
    Blood
    Understanding human hematopoietic stem cell fate control is important for its improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear because of technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, nonrandom process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes, and recycling endosomes, show preferential asymmetric cosegregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell-cycle length, differentiation, and stem cell marker expression, whereas asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.
  • Adult blood stem cell localization reflects the abundance of reported bone marrow niche cell types and their combinations
    Item type: Journal Article
    Kokkaliaris, Konstantinos D.; Kunz, Leo; Cabezas Wallscheid, Nina; et al. (2020)
    Blood
    The exact localization of hematopoietic stem cells (HSCs) in their native bone marrow (BM) microenvironment remains controversial, because multiple cell types have been reported to physically associate with HSCs. In this study, we comprehensively quantified HSC localization with up to 4 simultaneous (9 total) BM components in 152 full-bone sections from different bone types and 3 HSC reporter lines. We found adult femoral α-catulin-GFP+ or Mds1GFP/+Flt3Cre HSCs proximal to sinusoids, Cxcl12 stroma, megakaryocytes, and different combinations of those populations, but not proximal to bone, adipocyte, periarteriolar, or Schwann cells. Despite microanatomical differences in femurs and sterna, their adult α-catulin-GFP+ HSCs had similar distributions. Importantly, their microenvironmental localizations were not different from those of random dots, reflecting the relative abundance of imaged BM populations rather than active enrichment. Despite their functional heterogeneity, dormant label-retaining (LR) and non-LR hematopoietic stem and progenitor cells both had indistinguishable localization from α-catulin-GFP+ HSCs. In contrast, cycling juvenile BM HSCs preferentially located close to Cxcl12 stroma and farther from sinusoids/megakaryocytes. We expect our study to help resolve existing confusion regarding the exact localization of different HSC types, their physical association with described BM populations, and their tissue-wide combinations. © 2020 by The American Society of Hematology.
  • IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice
    Item type: Journal Article
    Kovtonyuk, Larisa V.; Caiado, Francisco; Garcia-Martin, Santiago; et al. (2022)
    Blood
    Aging is associated with impaired hematopoietic and immune function caused in part by decreased fitness in the hematopoietic stem cell (HSC) population and an increased myeloid differentiation bias. The reasons for this aging-associated HSC impairment are incompletely understood. Here we demonstrate that older specific pathogen free (SPF) wild-type (WT) mice in contrast to young SPF mice produce more interleukin-1a and interleukin-1b (IL-1a/b) in steady-state bone marrow (BM), with most of the IL-1a/b being derived from myeloid BM cells. Furthermore, blood from steady-state older SPF WT mice contains higher levels of microbe-associated molecular patterns, specifically TLR4 and TLR8 ligands. In addition, BM myeloid cells from older mice produce more IL-1b in vitro, and older mice show higher and more durable IL-1a/b responses upon stimulation with lipopolysaccharide in vivo. To test whether HSC aging is driven by IL-1a/b, we evaluated HSCs from IL-1 receptor 1 (IL-1R1) knockout (KO) mice. Indeed, older HSCs from IL-1R1KO mice show significantly mitigated aging-associated inflammatory signatures. Moreover, HSCs from older IL-1R1KO and from germ-free mice maintain unbiased lymphomyeloid hematopoietic differentiation upon transplantation, thus resembling this functionality of young HSCs. Importantly, in vivo antibiotic suppression of microbiota or pharmacologic blockade of IL-1 signaling in older WT mice was similarly sufficient to reverse myeloid-biased output of their HSC populations. Collectively, our data define the microbiome/IL-1/IL-1R1 axis as a key, self-sustaining and also therapeutically partially reversible driver of HSC inflammaging.
  • Nanoporous Substrates to Advance CAR-T Cell Production for Advanced Cell Therapies
    Item type: Other Conference Item
    Klotzsch, Enrico; Zünd, Tamara; Lickert, Sebastian; et al. (2023)
    Blood
  • Targeting Interleukin-2 to the Bone Marrow Stroma for Therapy of Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation
    Item type: Other Conference Item
    Schliemann, Christoph; Gutbrodt, Katrin L.; Kerkhoff, Andrea; et al. (2014)
    Blood
  • A Diet Rich in Alpha-Linolenic Acid Diminishes Atherosclerosis in Apolipoprotein E-Deficient Mice and Reduces Arachidonic Acid in Red Cell Membranes
    Item type: Conference Poster
    Matter, Christian M.R.; Lohmann, Christine; Richter, Eva; et al. (2008)
    Blood
Publications 1 - 10 of 79