title: High-resolution imaging and computational analysis of haematopoietic cell dynamics in vivo.
abstract: 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.
authors.affiliation: 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.
authors.forename: Claire S
authors.initials: CS
authors.lastname: Koechlein
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Harris
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Timothy K
authors.identifier: 0000-0002-9853-9869
authors.initials: TK
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Joi
authors.initials: J
authors.lastname: Weeks
authors.affiliation: 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.
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Fox
authors.affiliation: 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.
authors.forename: Bryan
authors.initials: B
authors.lastname: Zimdahl
authors.affiliation: 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.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: 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.
authors.forename: Allen
authors.initials: A
authors.lastname: Blevins
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Seung-Hye
authors.initials: SH
authors.lastname: Jung
authors.affiliation: 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.
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
authors.affiliation: San Diego Supercomputer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Chourasia
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Covert
authors.affiliation: 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.
authors.forename: Tannishtha
authors.initials: T
authors.lastname: Reya
mesh_terms: D000818:Animals; D058948:Cell Tracking; D003198:Computer Simulation; D003199:Computer Systems; D005260:Female; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D016601:RNA-Binding Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: C499059:Msi2h protein, mouse; D016601:RNA-Binding Proteins; D049452:Green Fluorescent Proteins