Adult stem cell lineage tracing and deep tissue imaging

Lineage tracing is a widely used method for understanding cellular dynamics in multicellular organisms during processes such as development, adult tissue maintenance, injury repair and tumorigenesis. Advances in tracing or tracking methods, from light microscopy-based live cell tracking to fluorescent label-tracing with two-photon microscopy, together with emerging tissue clearing strategies and intravital imaging approaches have enabled scientists to decipher adult stem and progenitor cell properties in various tissues and in a wide variety of biological processes. Although technical advances have enabled time-controlled genetic labeling and simultaneous live imaging, a number of obstacles still need to be overcome. In this review, we aim to provide an in-depth description of the traditional use of lineage tracing as well as current strategies and upcoming new methods of labeling and imaging. [BMB Reports 2015; 48(12): 655-667]

[1]  E. Stelzer,et al.  Live imaging of Tribolium castaneum embryonic development using light-sheet–based fluorescence microscopy , 2015, Nature Protocols.

[2]  Kristin Branson,et al.  Whole-central nervous system functional imaging in larval Drosophila , 2015, Nature Communications.

[3]  Willy Supatto,et al.  Whole-brain functional imaging with two-photon light-sheet microscopy , 2015, Nature Methods.

[4]  Misha B. Ahrens,et al.  Visualizing Whole-Brain Activity and Development at the Single-Cell Level Using Light-Sheet Microscopy , 2015, Neuron.

[5]  Incheol Seo,et al.  Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine , 2014, BMC Developmental Biology.

[6]  Victor G. Piazza,et al.  Quantitative imaging of cell dynamics in mouse embryos using light-sheet microscopy , 2014, Development.

[7]  Wesley R. Legant,et al.  Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution , 2014, Science.

[8]  Rajan P Kulkarni,et al.  Single-Cell Phenotyping within Transparent Intact Tissue through Whole-Body Clearing , 2014, Cell.

[9]  Shuo Diao,et al.  Through-skull fluorescence imaging of the brain in a new near-infrared window , 2014, Nature Photonics.

[10]  K. Deisseroth,et al.  Advanced CLARITY for rapid and high-resolution imaging of intact tissues , 2014, Nature Protocols.

[11]  Philip Greulich,et al.  Differentiation imbalance in single oesophageal progenitor cells causes clonal immortalization and field change , 2014, Nature Cell Biology.

[12]  Magdalena Zernicka-Goetz,et al.  Self-Organizing Properties of Mouse Pluripotent Cells Initiate Morphogenesis upon Implantation , 2014, Cell.

[13]  Hans Clevers,et al.  Intestinal crypt homeostasis revealed at single stem cell level by in vivo live-imaging , 2014, Nature.

[14]  Toby Xu,et al.  Single-chip CMUT-on-CMOS front-end system for real-time volumetric IVUS and ICE imaging , 2014, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[15]  R. Hesketh,et al.  Dual-modality gene reporter for in vivo imaging , 2013, Proceedings of the National Academy of Sciences.

[16]  H. Clevers,et al.  Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion , 2013, EMBO reports.

[17]  Hans Clevers,et al.  Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. , 2013, Cell stem cell.

[18]  Andrea Sottoriva,et al.  Defining Stem Cell Dynamics in Models of Intestinal Tumor Initiation , 2013, Science.

[19]  Simon Tavaré,et al.  Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. , 2013, Cell stem cell.

[20]  Justin Senseney,et al.  Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy , 2013, Nature Biotechnology.

[21]  Samantha A. Morris,et al.  The differential response to Fgf signalling in cells internalized at different times influences lineage segregation in preimplantation mouse embryos , 2013, Open Biology.

[22]  H. Clevers,et al.  Generation of BAC Transgenic Epithelial Organoids , 2013, PloS one.

[23]  H. Wiley,et al.  Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo , 2013, Oncogene.

[24]  David A. Scott,et al.  Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity , 2013, Cell.

[25]  C. Soderblom,et al.  Perivascular Fibroblasts Form the Fibrotic Scar after Contusive Spinal Cord Injury , 2013, The Journal of Neuroscience.

[26]  G. Church,et al.  CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering , 2013, Nature Biotechnology.

[27]  Benjamin D. Simons,et al.  Unravelling stem cell dynamics by lineage tracing , 2013, Nature Reviews Molecular Cell Biology.

[28]  M. Neeman,et al.  MRI reporter genes: applications for imaging of cell survival, proliferation, migration and differentiation , 2013, NMR in biomedicine.

[29]  S. Waldman,et al.  Colorectal cancer stem cells as biomarkers: Where it all starts? , 2013, Journal of surgical oncology.

[30]  H. Clevers,et al.  Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications , 2013, Science.

[31]  D. Piwnica-Worms,et al.  Illuminating cancer systems with genetically engineered mouse models and coupled luciferase reporters in vivo. , 2013, Cancer discovery.

[32]  Aaron S. Andalman,et al.  Structural and molecular interrogation of intact biological systems , 2013, Nature.

[33]  Jacco van Rheenen,et al.  Surgical implantation of an abdominal imaging window for intravital microscopy , 2013, Nature Protocols.

[34]  J. van Rheenen,et al.  Brief Report: Intravital Imaging of Cancer Stem Cell Plasticity in Mammary Tumors , 2012, Stem cells.

[35]  Lifeng Zhang,et al.  Imaging glioma initiation in vivo through a polished and reinforced thin-skull cranial window. , 2012, Journal of visualized experiments : JoVE.

[36]  Fa-An Chao,et al.  Structure and dynamics of a primordial catalytic fold generated by in vitro evolution , 2012, Nature chemical biology.

[37]  V. Runge,et al.  MRI contrast agents: Basic chemistry and safety , 2012, Journal of magnetic resonance imaging : JMRI.

[38]  C. Blanpain,et al.  Multipotent and unipotent progenitors contribute to prostate postnatal development , 2012, Nature Cell Biology.

[39]  Frank Bradke,et al.  Three-dimensional imaging of solvent-cleared organs using 3DISCO , 2012, Nature Protocols.

[40]  Hans Clevers,et al.  Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas , 2012, Science.

[41]  Zeger Debyser,et al.  Quantitative evaluation of MRI-based tracking of ferritin-labeled endogenous neural stem cell progeny in rodent brain , 2012, NeuroImage.

[42]  Benjamin D. Simons,et al.  Defining the mode of tumour growth by clonal analysis , 2012, Nature.

[43]  Jacco van Rheenen,et al.  Intravital imaging of cell signaling in mice , 2012 .

[44]  T. Schroeder,et al.  Advances in tracking hematopoiesis at the single-cell level , 2012, Current opinion in hematology.

[45]  R. Weigert.  Welcome to IntraVital , 2012 .

[46]  Philipp J. Keller,et al.  Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy , 2012, Nature Methods.

[47]  Jae-Hyun Park,et al.  Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. , 2012, Cancer cell.

[48]  L. Parada,et al.  Malignant Glioma: Lessons from Genomics, Mouse Models, and Stem Cells , 2012, Cell.

[49]  R. Weiler,et al.  Chemical Clearing and Dehydration of GFP Expressing Mouse Brains , 2012, PloS one.

[50]  Fei Li,et al.  In vivo magnetic resonance imaging tracking of SPIO‐labeled human umbilical cord mesenchymal stem cells , 2012, Journal of cellular biochemistry.

[51]  Frank Bradke,et al.  Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury , 2011, Nature Medicine.

[52]  H. Clevers,et al.  Controlled gene expression in primary Lgr5 organoid cultures , 2011, Nature Methods.

[53]  Atsushi Miyawaki,et al.  Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain , 2011, Nature Neuroscience.

[54]  Philipp J. Keller,et al.  Digital scanned laser light-sheet fluorescence microscopy (DSLM) of zebrafish and Drosophila embryonic development. , 2011, Cold Spring Harbor protocols.

[55]  H. Okamura,et al.  Accurate Determination of S-Phase Fraction in Proliferative Cells by Dual Fluorescence and Peroxidase Immunohistochemistry with 5-Bromo-2′-Deoxyuridine (BrdU) and Ki67 Antibodies , 2011, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[56]  Sean G. Megason,et al.  Current challenges in image analysis for in toto imaging of zebrafish , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[57]  Karthikeyan Subramani,et al.  Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. , 2011, Chemical reviews.

[58]  Allon M Klein,et al.  Intestinal Stem Cell Replacement Follows a Pattern of Neutral Drift , 2010, Science.

[59]  Hans Clevers,et al.  Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells , 2010, Cell.

[60]  Monya Baker,et al.  Cellular imaging: Taking a long, hard look , 2010, Nature.

[61]  Allon M. Klein,et al.  Mouse germ line stem cells undergo rapid and stochastic turnover. , 2010, Cell stem cell.

[62]  Monika Sramkova,et al.  Intravital microscopy: a novel tool to study cell biology in living animals , 2010, Histochemistry and Cell Biology.

[63]  Samantha A. Morris,et al.  Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo , 2010, Proceedings of the National Academy of Sciences.

[64]  Andrew R. Cohen,et al.  Computational prediction of neural progenitor cell fates , 2010, Nature Methods.

[65]  Allon M. Klein,et al.  The ordered architecture of murine ear epidermis is maintained by progenitor cells with random fate. , 2010, Developmental cell.

[66]  Hans Clevers,et al.  Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. , 2010, Cell stem cell.

[67]  K. Bhakoo,et al.  In vivo multimodal imaging of stem cell transplantation in a rodent model of Parkinson's disease , 2009, Journal of Neuroscience Methods.

[68]  A. Charest,et al.  A Cre/LoxP conditional luciferase reporter transgenic mouse for bioluminescence monitoring of tumorigenesis , 2009, Genesis.

[69]  H. Clevers,et al.  Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche , 2009, Nature.

[70]  Rakesh K Jain,et al.  In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts , 2009, Nature Methods.

[71]  Jacco van Rheenen,et al.  Intravital imaging of metastatic behavior through a mammary imaging window , 2008, Nature Methods.

[72]  Juan M. Guayasamin,et al.  Phylogenetic relationships of glassfrogs (Centrolenidae) based on mitochondrial and nuclear genes. , 2008, Molecular phylogenetics and evolution.

[73]  Liu Yang,et al.  In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. , 2008, Joint, bone, spine : revue du rhumatisme.

[74]  Timm Schroeder,et al.  Imaging stem-cell-driven regeneration in mammals , 2008, Nature.

[75]  H. Dodt,et al.  Ultramicroscopy: 3D reconstruction of large microscopical specimens , 2008, Journal of biophotonics.

[76]  R. W. Draft,et al.  Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system , 2007, Nature.

[77]  H. Clevers,et al.  Identification of stem cells in small intestine and colon by marker gene Lgr5 , 2007, Nature.

[78]  A. Schierloh,et al.  Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain , 2007, Nature Methods.

[79]  Keren Ziv,et al.  MRI detection of transcriptional regulation of gene expression in transgenic mice , 2007, Nature Medicine.

[80]  Yarong Wang,et al.  Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. , 2007, Cancer research.

[81]  Benjamin D. Simons,et al.  A single type of progenitor cell maintains normal epidermis , 2007, Nature.

[82]  H. Clevers,et al.  The Intestinal Wnt/TCF Signature. , 2007, Gastroenterology.

[83]  K. F. Perry,et al.  Metabolic biotinylation of cell surface receptors for in vivo imaging , 2006, Nature Methods.

[84]  Kathryn Sharer,et al.  In vivo detection of single cells by MRI , 2006, Magnetic resonance in medicine.

[85]  Jane Q. Nguyen,et al.  Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis , 2005, Nature Medicine.

[86]  Arend Heerschap,et al.  Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy , 2005, Nature Biotechnology.

[87]  Xunbin Wei,et al.  In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment , 2005, Nature.

[88]  Clifford M. Babbey,et al.  Performance comparison between the high‐speed Yokogawa spinning disc confocal system and single‐point scanning confocal systems , 2005, Journal of microscopy.

[89]  B. Klaunberg,et al.  In vivo bioluminescence imaging. , 2004, Comparative medicine.

[90]  F. Del Bene,et al.  Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy , 2004, Science.

[91]  Scott E. Fraser,et al.  Digitizing life at the level of the cell: high-performance laser-scanning microscopy and image analysis for in toto imaging of development , 2003, Mechanisms of Development.

[92]  Scott E. Fraser,et al.  MRI: volumetric imaging for vital imaging and atlas construction. , 2003, Nature reviews. Molecular cell biology.

[93]  Hans Clevers,et al.  The β-Catenin/TCF-4 Complex Imposes a Crypt Progenitor Phenotype on Colorectal Cancer Cells , 2002, Cell.

[94]  Meng Yang,et al.  Direct external imaging of nascent cancer, tumor progression, angiogenesis, and metastasis on internal organs in the fluorescent orthotopic model , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[95]  Shankar Srinivas,et al.  Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus , 2001, BMC Developmental Biology.

[96]  Caiying Guo,et al.  Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon cre‐mediated excision , 2000, Genesis.

[97]  K. Johnson Bowles,et al.  Taking a Long, Hard Look , 2000, Afterimage.

[98]  S. Goderie,et al.  Intrinsic programs of patterned cell lineages in isolated vertebrate CNS ventricular zone cells. , 1998, Development.

[99]  P Chambon,et al.  Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. , 1997, Biochemical and biophysical research communications.

[100]  A. Berns,et al.  Cre-mediated somatic site-specific recombination in mice. , 1997, Nucleic acids research.

[101]  David J. Anderson,et al.  Subregion- and Cell Type–Restricted Gene Knockout in Mouse Brain , 1996, Cell.

[102]  K. Messmer,et al.  Dorsal skinfold chamber technique for intravital microscopy in nude mice. , 1993, The American journal of pathology.

[103]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[104]  N. Munakata.  [Genetics of Caenorhabditis elegans]. , 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[105]  C. Potten,et al.  Double Labelling With Bromodeoxyuridine and (3H)‐Thymidine of Proliferative Cells In Small Intestinal Epithelium In Steady State and After Irradiation , 1988, Cell and tissue kinetics.

[106]  Michael W. Miller,et al.  Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system , 1988, Brain Research.

[107]  D. Agard,et al.  The use of a charge-coupled device for quantitative optical microscopy of biological structures. , 1987, Science.

[108]  A. de Fazio,et al.  Immunohistochemical identification of proliferating cells in organ culture using bromodeoxyuridine and a monoclonal antibody. , 1986, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[109]  P. Rabinovitch,et al.  Cell Cycle Kinetics By Brdu‐Hoechst Flow Cytometry: an Alternative to the Differential Metaphase Labelling Technique , 1985, Cell and tissue kinetics.

[110]  R. Hoess,et al.  Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. , 1984, The Journal of biological chemistry.

[111]  J. Sulston,et al.  The embryonic cell lineage of the nematode Caenorhabditis elegans. , 1983, Developmental biology.

[112]  J. Gray,et al.  Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[113]  H. Gratzner,et al.  Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. , 1982, Science.

[114]  D. Hirsh,et al.  The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. , 1979, Developmental biology.

[115]  J. Sulston,et al.  Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. , 1977, Developmental biology.

[116]  I. D. Abella,et al.  Optical Double-Photon Absorption in Cesium Vapor , 1962 .

[117]  C. Garrett,et al.  Two-Photon Excitation in CaF 2 : Eu 2+ , 1961 .

[118]  S WOOD,et al.  Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. , 1958, A.M.A. archives of pathology.

[119]  S. Kit,et al.  Effect of 5-bromodeoxyuridine on deoxyribonucleic acid-thymine synthesis and cell metabolism of lymphatic tissues and tumors. , 1958, Cancer research.

[120]  M. Krupa,et al.  Allocation of inner cells to epiblast vs primitive endoderm in the mouse embryo is biased but not determined by the round of asymmetric divisions (8→16- and 16→32-cells). , 2014, Developmental biology.

[121]  J. Sanes,et al.  Improved tools for the Brainbow toolbox. , 2013, Nature methods.

[122]  Ralph Weissleder,et al.  Intravital Imaging , 2011, Cell.

[123]  H. Clevers,et al.  Very long-term self-renewal of small intestine, colon, and hair follicles from cycling Lgr5+ve stem cells. , 2008, Cold Spring Harbor symposia on quantitative biology.

[124]  A. Hall,et al.  Two-versus one photon excitation laser scanning microscopy: critical importance of excitation wavelength. , 2007, Frontiers in bioscience : a journal and virtual library.

[125]  T. Schumacher,et al.  BMC Biotechnology BioMed Central Methodology article Intravital imaging of fluorescent markers and FRET probes by DNA tattooing , 2007 .

[126]  M. Makale.  Intravital imaging and cell invasion. , 2007, Methods in enzymology.

[127]  F. Beuschlein,et al.  Expression and spatio-temporal distribution of differentiation and proliferation markers during mouse adrenal development. , 2007, Gene expression patterns : GEP.

[128]  José-Angel Conchello,et al.  Fluorescence microscopy , 2005, Nature Methods.

[129]  C. Garrett,et al.  Two-photon excitation in CaF2:Eu2+ , 2003 .

[130]  A. Szalay,et al.  Imaging of light emission from the expression of luciferases in living cells and organisms: a review. , 2002, Luminescence : the journal of biological and chemical luminescence.

[131]  Y Fujiwara,et al.  Activation of EGFP expression by Cre-mediated excision in a new ROSA26 reporter mouse strain. , 2001, Blood.

[132]  J A Dent,et al.  A whole-mount immunocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus. , 1989, Development.

[133]  J. Trent,et al.  Cell cycle analysis using bromodeoxyuridine: comparison of methods for analysis of total cell transit time. , 1986, Cancer genetics and cytogenetics.

[134]  J W Gray,et al.  Cell cycle analysis using flow cytometry. , 1986, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[135]  Werner Spalteholz,et al.  Über das Durchsichtigmachen von menschlichen und tierischen Präparaten und seine theoretischen Bedingungen : nebst Anhang : Über Knochenfärbung , 1914 .