66 results found
Tjin G, Flores-Figueroa E, Duarte D, et al., 2019, Imaging methods used to study mouse and human HSC niches: Current and emerging technologies., Bone, Vol: 119, Pages: 19-35
Bone marrow contains numerous different cell types arising from hematopoietic stem cells (HSCs) and non-hematopoietic mesenchymal/skeletal stem cells, in addition to other cell types such as endothelial cells- these non-hematopoietic cells are commonly referred to as stromal cells or microenvironment cells. HSC function is intimately linked to complex signals integrated by their niches, formed by combinations of hematopoietic and stromal cells. Studies of hematopoietic cells have been significantly advanced by flow cytometry methods, enabling the quantitation of each cell type in normal and perturbed situations, in addition to the isolation of these cells for molecular and functional studies. Less is known, however, about the specific niches for distinct developing hematopoietic lineages, or the changes occurring in the niche size and function in these distinct anatomical sites in the bone marrow under stress situations and ageing. Significant advances in imaging technology during the last decade have permitted studies of HSC niches in mice. Additional imaging technologies are emerging that will facilitate the study of human HSC niches in trephine BM biopsies. Here we provide an overview of imaging technologies used to study HSC niches, in addition to highlighting emerging technology that will help us to more precisely identify and characterize HSC niches in normal and diseased states.
Duarte D, Amarteifio S, Ang H, et al., 2018, Defining the in vivo characteristics of acute myeloid leukemia cells behavior by intravital imaging., Immunol Cell Biol
The majority of acute myeloid leukemia (AML) patients have a poor response to conventional chemotherapy. The survival of chemoresistant cells is thought to depend on leukemia-bone marrow (BM) microenvironment interactions, which are not well understood. The CXCL12/CXCR4 axis has been proposed to support AML growth but was not studied at the single AML cell level. We recently showed that T-cell acute lymphoblastic leukemia (T-ALL) cells are highly motile in the BM; however, the characteristics of AML cell migration within the BM remain undefined. Here, we characterize the in vivo migratory behavior of AML cells and their response to chemotherapy and CXCR4 antagonism, using high-resolution 2-photon and confocal intravital microscopy of mouse calvarium BM and the well-established MLL-AF9-driven AML mouse model. We used the Notch1-driven T-ALL model as a benchmark comparison and AMD3100 for CXCR4 antagonism experiments. We show that AML cells are migratory, and in contrast with T-ALL, chemoresistant AML cells become less motile. Moreover, and in contrast with T-ALL, the in vivo exploratory behavior of expanding and chemoresistant AML cells is unaffected by AMD3100. These results expand our understanding of AML cells-BM microenvironment interactions, highlighting unique traits of leukemia of different lineages.
Brown E, Carlin LM, Nerlov C, et al., 2018, Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels., Life Sci Alliance, Vol: 1
Platelets, cells central to hemostasis and thrombosis, are formed from parent cell megakaryocytes. Whilst the process is highly efficient in vivo, our ability to generate them in vitro is still remarkably inefficient. We proposed that greater understanding of the process in vivo is needed and used an imaging approach, intravital correlative light-electron microscopy, to visualize platelet generation in bone marrow in the living mouse. In contrast to current understanding we found that most megakaryocytes enter the sinusoidal space as large protrusions rather than extruding fine proplatelet extensions. The mechanism for large protrusion migration also differed from that of proplatelet extension. In vitro, proplatelets extend by sliding of dense bundles of microtubules, whereas in vivo our data showed an absence of microtubule bundles in the large protrusion, but the presence of multiple fusion points between the internal membrane and the plasma membrane, at the leading edge of the protruding cell. Mass membrane fusion therefore drives megakaryocyte large protrusions into the sinusoid, significantly revising our understanding of the fundamental biology of platelet formation in vivo.
Willis AR, Torraca V, Gomes MC, et al., 2018, Shigella-Induced Emergency Granulopoiesis Protects Zebrafish Larvae from Secondary Infection, MBIO, Vol: 9, ISSN: 2150-7511
Khan AB, Carpenter B, Santos e Sousa P, et al., 2018, Redirection to the bone marrow improves T cell persistence and antitumor functions, JOURNAL OF CLINICAL INVESTIGATION, Vol: 128, Pages: 2010-2024, ISSN: 0021-9738
Duarte D, Hawkins ED, Lo Celso C, 2018, The interplay of leukemia cells and the bone marrow microenvironment, Blood, Vol: 131, Pages: 1507-1511, ISSN: 1528-0020
The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models have advanced our comprehension of leukemia-microenvironment crosstalk and have potential implications for development of novel treatment options.
Akinduro O, Weber TS, Ang H, et al., 2018, Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space., Nat Commun, Vol: 9
Leukaemia progressively invades bone marrow (BM), outcompeting healthy haematopoiesis by mechanisms that are not fully understood. Combining cell number measurements with a short-timescale dual pulse labelling method, we simultaneously determine the proliferation dynamics of primitive haematopoietic compartments and acute myeloid leukaemia (AML). We observe an unchanging proportion of AML cells entering S phase per hour throughout disease progression, with substantial BM egress at high levels of infiltration. For healthy haematopoiesis, we find haematopoietic stem cells (HSCs) make a significant contribution to cell production, but we phenotypically identify a quiescent subpopulation with enhanced engraftment ability. During AML progression, we observe that multipotent progenitors maintain a constant proportion entering S phase per hour, despite a dramatic decrease in the overall population size. Primitive populations are lost from BM with kinetics that are consistent with ousting irrespective of cell cycle state, with the exception of the quiescent HSC subpopulation, which is more resistant to elimination.
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-+, ISSN: 1934-5909
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
MacLean AL, Smith MA, Liepe J, et al., 2017, Single Cell Phenotyping Reveals Heterogeneity Among Hematopoietic Stem Cells Following Infection, STEM CELLS, Vol: 35, Pages: 2292-2304, ISSN: 1066-5099
Athanasiou D, Edgar LT, Jafarnejad M, et al., 2017, The passive biomechanics of human pelvic collecting lymphatic vessels, PLOS ONE, Vol: 12, ISSN: 1932-6203
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
Beerman I, Luis TC, Singbrant S, et al., 2017, The evolving view of the hematopoietic stem cell niche, EXPERIMENTAL HEMATOLOGY, Vol: 50, Pages: 22-26, ISSN: 0301-472X
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
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
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
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.
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.
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, 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, 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
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
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
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
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
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
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
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