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Tytuł:
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High-resolution imaging and computational analysis of haematopoietic cell dynamics in vivo.
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Autorzy:
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Koechlein CS; Departments of Pharmacology and Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.; Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.
Harris JR; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Lee TK; Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
Weeks J; Departments of Pharmacology and Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.; Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.
Fox RG; Departments of Pharmacology and Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.; Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.
Zimdahl B; Departments of Pharmacology and Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.; Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ito T; Departments of Pharmacology and Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.; Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Blevins A; Departments of Pharmacology and Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.; Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.
Jung SH; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Chute JP; Division of Cellular Therapy, Duke University Medical Center, Durham, North Carolina 27710, USA.; Division of Hematology Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
Chourasia A; San Diego Supercomputer Center, University of California, San Diego, La Jolla, California 92093, USA.
Covert MW; Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
Reya T; Departments of Pharmacology and Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.; Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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Źródło:
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Nature communications [Nat Commun] 2016 Jul 18; Vol. 7, pp. 12169. Date of Electronic Publication: 2016 Jul 18.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: [London] : Nature Pub. Group
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MeSH Terms:
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Computer Simulation*
Imaging, Three-Dimensional*
Hematopoietic Stem Cells/*cytology
Animals ; Cell Tracking ; Computer Systems ; Female ; Genes, Reporter ; Green Fluorescent Proteins/metabolism ; Male ; Mice ; RNA-Binding Proteins/metabolism ; Time Factors
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References:
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Grant Information:
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K99 CA125994 United States CA NCI NIH HHS; T32 GM007184 United States GM NIGMS NIH HHS; R00 CA125994 United States CA NCI NIH HHS; R01 DK072234 United States DK NIDDK NIH HHS; DP1 OD006430 United States OD NIH HHS; T32 HL086344 United States HL NHLBI NIH HHS; P50 GM107615 United States GM NIGMS NIH HHS; DP1 CA174422 United States CA NCI NIH HHS; T32 EB001630 United States EB NIBIB NIH HHS; T32 GM008412 United States GM NIGMS NIH HHS; T32 GM007752 United States GM NIGMS NIH HHS; U19 AI067798 United States AI NIAID NIH HHS; T32 CA009523 United States CA NCI NIH HHS; R35 CA197699 United States CA NCI NIH HHS; DP1 OD006413 United States OD NIH HHS
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Substance Nomenclature:
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0 (Msi2h protein, mouse)
0 (RNA-Binding Proteins)
147336-22-9 (Green Fluorescent Proteins)
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Entry Date(s):
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Date Created: 20160719 Date Completed: 20180827 Latest Revision: 20181113
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Update Code:
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20240104
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PubMed Central ID:
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PMC4960315
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DOI:
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10.1038/ncomms12169
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PMID:
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27425143
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Although we know a great deal about the phenotype and function of haematopoietic stem/progenitor cells, a major challenge has been mapping their dynamic behaviour within living systems. Here we describe a strategy to image cells in vivo with high spatial and temporal resolution, and quantify their interactions using a high-throughput computational approach. Using these tools, and a new Msi2 reporter model, we show that haematopoietic stem/progenitor cells display preferential spatial affinity for contacting the vascular niche, and a temporal affinity for making stable associations with these cells. These preferences are markedly diminished as cells mature, suggesting that programs that control differentiation state are key determinants of spatiotemporal behaviour, and thus dictate the signals a cell receives from specific microenvironmental domains. These collectively demonstrate that high-resolution imaging coupled with computational analysis can provide new biological insight, and may in the long term enable creation of a dynamic atlas of cells within their native microenvironment.
