58 results found
Duarte D, Hawkins ED, Akinduro O, et al., 2018, Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML., Cell Stem Cell, Vol: 22, Pages: 64-77.e6
Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression leads to differential remodeling of vasculature in central and endosteal bone marrow regions. Endosteal AML cells produce pro-inflammatory and anti-angiogenic cytokines and gradually degrade endosteal endothelium, stromal cells, and osteoblastic cells, whereas central marrow remains vascularized and splenic vascular niches expand. Remodeled endosteal regions have reduced capacity to support non-leukemic HSCs, correlating with loss of normal hematopoiesis. Preserving endosteal endothelium with the small molecule deferoxamine or a genetic approach rescues HSCs loss, promotes chemotherapeutic efficacy, and enhances survival. These findings suggest that preventing degradation of the endosteal vasculature may improve current paradigms for treating AML.
Beerman I, Luis TC, Singbrant S, et al., 2017, The evolving view of the hematopoietic stem cell niche., Exp Hematol, Vol: 50, Pages: 22-26
Hematopoietic stem cells (HSCs) reside in specialized microenvironments known as niches. The niche is essential to support HSC function and to maintain a correct balance between self-renewal and differentiation. Recent advances in defining different mesenchymal and endothelial bone marrow cell populations, as well as hematopoietic stem and progenitor cells, greatly enhanced our understanding of these niches and of the molecular mechanisms by which they regulate HSC function. In addition to the role in maintaining HSC homeostasis, the niche has also been implicated in the pathogenesis of blood disorders including hematological malignancies. Characterizing the extrinsic regulators and the cellular context in which the niches interact with HSCs will be crucial to define new strategies to enhance blood regeneration. Furthermore, a better understanding of the role of the niche in leukemia development will open new possibilities for the treatment of these disorders by using therapies aiming to target the leukemic niche specifically. To update on recent findings on this topic, the International Society for Experimental Hematology (ISEH) organized a webinar, presented by Prof. Sean J. Morrison and Dr. Simón Méndez-Ferrer and moderated by Dr. Cristina Lo Celso, entitled "The evolving view of the hematopoietic stem cell niche," which we summarize here.
Lo Celso C, 2017, Revealing the inner workings of human HSC adhesion, BLOOD, Vol: 129, Pages: 921-922, ISSN: 0006-4971
MacLean AL, Lo Celso C, Stumpf MPH, 2017, Concise Review: Stem Cell Population Biology: Insights from Hematopoiesis, STEM CELLS, Vol: 35, Pages: 80-88, ISSN: 1066-5099
Secklehner J, Lo Celso C, Carlin LM, 2017, Intravital microscopy in historic and contemporary immunology, IMMUNOLOGY AND CELL BIOLOGY, Vol: 95, Pages: 506-513, ISSN: 0818-9641
Wang W, Fujii H, Kim HJ, et al., 2017, Enhanced human hematopoietic stem and progenitor cell engraftment by blocking donor T cell-mediated TNF alpha signaling, SCIENCE TRANSLATIONAL MEDICINE, Vol: 9, ISSN: 1946-6234
Hawkins ED, Duarte D, Akinduro O, et al., 2016, T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments, NATURE, Vol: 538, Pages: 518-+, ISSN: 0028-0836
Khorshed RA, Lo Celso C, 2016, MACHINE LEARNING CLASSIFICATION OF COMPLEX VASCULATURE STRUCTURES FROM IN-VIVO BONE MARROW 3D DATA, IEEE 13th International Symposium on Biomedical Imaging (ISBI), Publisher: IEEE, Pages: 1217-1220, ISSN: 1945-7928
Khorshed RA, Lo Celso C, 2016, Automated identification and measurement of Hematopoietic Stem Cells in 3D Intravital Microscopy Data, Microscopy and Analysis, Editors: Stanciu, Publisher: InTech, ISBN: 978-953-51-2578-5
Image analysis and quantification of Haematopoietic stem cells (HSCs) position within their surrounding microenvironment in the bone marrow is a fast growing area of research, as it holds the key to understanding the dynamics of HSC-niche interactions and their multiple implications in normal tissue development and in response to various stress events. However, this area of research is very challenging due to the complex cellular structure of such images. Therefore, automated image analysis tools are required to simplify the biological interpretation of 3D HSC microenvironment images. In this chapter, we describe how 3D intravital microscopy data can be visualised and analysed using a computational method that allows the automated quantification of HSC position relative to surrounding niche components.
Lo Celso C, Hawkins ED, Duarte D, et al., 2016, Intravital Microscopy Reveals Fundamental Differences in the Interaction of Stem Cells and T Acute Lymphoblastic Leukaemia with the Bone Marrow Microenvironment, 58th Annual Meeting and Exposition of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Silberstein L, Goncalves KA, Kharchenko PV, et al., 2016, Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators., Cell Stem Cell, Vol: 19, Pages: 530-543
Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function.
Vainieri ML, Blagborough AM, MacLean AL, et al., 2016, Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points, OPEN BIOLOGY, Vol: 6, ISSN: 2046-2441
Khorshed RA, Hawkins ED, Duarte D, et al., 2015, Automated Identification and Localization of Hematopoietic Stem Cells in 3D Intravital Microscopy Data, STEM CELL REPORTS, Vol: 5, Pages: 139-153, ISSN: 2213-6711
Batista S, Maniati E, Reynolds LE, et al., 2014, Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723
Rashidi NM, Lo Celso C, 2014, Flying back to the nest: Intravital microscopy reveals how the niche can induce stemness., Intravital, Vol: 3, ISSN: 2165-9087
Rashidi NM, Scott MK, Scherf N, et al., 2014, In vivo time-lapse imaging shows diverse niche engagement by quiescent and naturally activated hematopoietic stem cells, BLOOD, Vol: 124, Pages: 79-83, ISSN: 0006-4971
Scott MK, Akinduro O, Lo Celso C, 2014, In Vivo 4-Dimensional Tracking of Hematopoietic Stem and Progenitor Cells in Adult Mouse Calvarial Bone Marrow, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X
Carlson AL, Fujisaki J, Wu J, et al., 2013, Tracking Single Cells in Live Animals Using a Photoconvertible Near-Infrared Cell Membrane Label, PLOS ONE, Vol: 8, ISSN: 1932-6203
Fink J, Kent D, Li J, et al., 2013, HOMOZYGOUS JAK2V617F DRIVES RAPID HEMATOPOIETIC STEM CELL PROLIFERATION AND DIFFERENTIATION AT THE EXPENSE OF SELF-RENEWAL, 42nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology-and-Stem-Cells (ISEH), Publisher: ELSEVIER SCIENCE INC, Pages: S15-S15, ISSN: 0301-472X
Hawkins ED, Lo Celso C, 2013, Subdivision of bone marrow microenvironments: purpose built homes for haematopoietic stem cells, EMBO JOURNAL, Vol: 32, Pages: 176-177, ISSN: 0261-4189
Joseph C, Quach JM, Walkley CR, et al., 2013, Deciphering Hematopoietic Stem Cells in Their Niches: A Critical Appraisal of Genetic Models, Lineage Tracing, and Imaging Strategies, CELL STEM CELL, Vol: 13, Pages: 520-533, ISSN: 1934-5909
Lo Celso C, 2013, IN VIVO IMAGING OF QUIESCENT AND PHYSIOLOGICALLY ACTIVATED HAEMATOPOIETIC STEM CELLS, 42nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology-and-Stem-Cells (ISEH), Publisher: ELSEVIER SCIENCE INC, Pages: S4-S4, ISSN: 0301-472X
MacLean AL, Lo Celso C, Stumpf MPH, 2013, Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 10, ISSN: 1742-5689
Progatzky F, Dallman MJ, Lo Celso C, 2013, From seeing to believing: labelling strategies for in vivo cell-tracking experiments, INTERFACE FOCUS, Vol: 3, ISSN: 2042-8898
Roeder I, Krinner A, Scherf N, et al., 2013, QUANTIFICATION OF STEM CELL/NICHE INTERACTIONS BY COUPLING IN VIVO IMAGING AND IN SILICO SIMULATION, 42nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology-and-Stem-Cells (ISEH), Publisher: ELSEVIER SCIENCE INC, Pages: S31-S31, ISSN: 0301-472X
Barrett O, Sottocornola R, Lo Celso C, 2012, In vivo imaging of hematopoietic stem cells in the bone marrow niche., Methods Mol Biol, Vol: 916, Pages: 231-242
Even though hematopoietic stem cells (HSC) are amongst the first somatic stem cells exploited for therapeutic purposes, their application is still limited by the inability to expand them ex vivo without impairing their function. Moreover, it has recently emerged that several types of leukemia develop and relapse through complex interactions with bone marrow (BM) components and may directly affect the HSC and their niche. Increasing attention has therefore been dedicated to the BM microenvironment the HSC reside in, with the view that a better understanding of the molecular regulators of HSC-niche interaction in vivo will allow improving HSC mobilization, collection and transplantation and provide clues for the development of innovative leukemia treatments. This chapter focuses on a recently established technique for the visualization of transplanted hematopoietic stem and progenitor cells (HSPC) within the calvarium bone marrow of live mice (Lo Celso et al. Nature 457:92-96, 2007). Intravital microscopy is a rapidly developing field, driven by constant improvement in both detection technologies (i.e., spatial resolution, depth of penetration, spectral definition) and probe availability (i.e., increasingly sophisticated genetic and chemical reporter systems). We therefore discuss the current limitations and challenges related to intravital microscopy of the HSC niche and introduce a number of potential imaging approaches, which could be promising candidates for future development of this technique.
Sottocornola R, Lo Celso C, 2012, Dormancy in the stem cell niche, STEM CELL RESEARCH & THERAPY, Vol: 3, ISSN: 1757-6512
Cornejo MG, Mabialah V, Sykes SM, et al., 2011, Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification, BLOOD, Vol: 118, Pages: 1264-1273, ISSN: 0006-4971
Fujisaki J, Wu J, Carlson AL, et al., 2011, In vivo imaging of T-reg cells providing immune privilege to the haematopoietic stem-cell niche, NATURE, Vol: 474, Pages: 216-U256, ISSN: 0028-0836
Lane SW, Wang YJ, Lo Celso C, et al., 2011, Differential niche and Wnt requirements during acute myeloid leukemia progression, BLOOD, Vol: 118, Pages: 2849-2856, ISSN: 0006-4971
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