Automated Cell Lineage Construction: A Rapid Method to Analyze Clonal Development Established with Murine Neural Progenitor Cells

Understanding cell lineage relationships is fundamental to understanding development, and can shed light on disease etiology and progression. We present a method for automated tracking of lineages of proliferative, migrating cells from a sequence of images. The method is applicable to image sequences gathered either in vitro or in vivo. Currently, generating lineage trees from progenitor cells over time is a tedious, manual process, which limits the number of cell measurements that can be practically analyzed. In contrast, the automated method is rapid and easily applied, and produces a wealth of measurements including the precise position, shape, cell-cell contacts, motility and ancestry of each cell in every frame, and accurate timings of critical events, e.g. mitosis and cell death. Furthermore, it automatically produces graphical output that is immediately accessible. Application to clonal development of mouse neural progenitor cells growing in cell culture reveals complex changes in cell cycle rates during neuron and glia production. The method enables a level of quantitative analysis of cell behavior over time that was previously infeasible.

[1]  G. Nemhauser,et al.  Integer Programming , 2020 .

[2]  Bui Tuong Phong.  Illumination for computer generated pictures , 1975, Commun. ACM.

[3]  J. Sulston.  Post-embryonic development in the ventral cord of Caenorhabditis elegans. , 1976, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

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

[5]  N. Otsu.  A threshold selection method from gray level histograms , 1979 .

[6]  J E Sulston,et al.  Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans. , 1981, Developmental biology.

[7]  Martin Chalfie,et al.  Mutations that lead to reiterations in the cell lineages of C. elegans , 1981, Cell.

[8]  Luc Vincent,et al.  Watersheds in Digital Spaces: An Efficient Algorithm Based on Immersion Simulations , 1991, IEEE Trans. Pattern Anal. Mach. Intell..

[9]  M E Hatten,et al.  Motility and cytoskeletal organization of migrating cerebellar granule neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  V. Caviness,et al.  Early ontogeny of the secondary proliferative population of the embryonic murine cerebral wall , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  Kenong Wu,et al.  Live cell image segmentation , 1995, IEEE Transactions on Biomedical Engineering.

[12]  Krishna R. Pattipati,et al.  Multiassignment for tracking a large number of overlapping objects , 1997, Optics & Photonics.

[13]  Michael Isard,et al.  Active Contours: The Application of Techniques from Graphics, Vision, Control Theory and Statistics to Visual Tracking of Shapes in Motion , 2000 .

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

[15]  Yasuda,et al.  Towards Automatic Construction of Cell-Lineage of C. elegans from Nomarski DIC Microscope Images. , 1999, Genome informatics. Workshop on Genome Informatics.

[16]  P. Rakic,et al.  Organotypic slice cultures for analysis of proliferation, cell death, and migration in the embryonic neocortex. , 1999, Brain research. Brain research protocols.

[17]  James A. Sethian,et al.  Level Set Methods and Fast Marching Methods , 1999 .

[18]  S. Goderie,et al.  Timing of CNS Cell Generation A Programmed Sequence of Neuron and Glial Cell Production from Isolated Murine Cortical Stem Cells , 2000, Neuron.

[19]  T. Weissman,et al.  Neurons derived from radial glial cells establish radial units in neocortex , 2001, Nature.

[20]  H. Okano,et al.  Asymmetric Inheritance of Radial Glial Fibers by Cortical Neurons , 2001, Neuron.

[21]  Jaime Grutzendler,et al.  Two modes of radial migration in early development of the cerebral cortex , 2001, Nature Neuroscience.

[22]  M. T. Shipley,et al.  Unique neuronal tracers show migration and differentiation of SVZ progenitors in organotypic slices. , 2001, Journal of neurobiology.

[23]  Scott T. Acton,et al.  Tracking leukocytes in vivo with shape and size constrained active contours , 2002, IEEE Transactions on Medical Imaging.

[24]  D. Dormann,et al.  Simultaneous quantification of cell motility and protein-membrane-association using active contours. , 2002, Cell motility and the cytoskeleton.

[25]  Vannary Meas-Yedid,et al.  Segmentation and tracking of migrating cells in videomicroscopy with parametric active contours: a tool for cell-based drug testing , 2002, IEEE Transactions on Medical Imaging.

[26]  T Tarui,et al.  Cell output, cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process. , 2003, Cerebral cortex.

[27]  Hans-Peter Meinzer,et al.  ALES: Cell Lineage Analysis and Mapping of Developmental Events , 2003, Bioinform..

[28]  Robert T. Collins,et al.  Mean-shift blob tracking through scale space , 2003, 2003 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2003. Proceedings..

[29]  C Wählby,et al.  Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections , 2004, Journal of microscopy.

[30]  Christophe Zimmer,et al.  Segmenting and tracking fluorescent cells in dynamic 3-D microscopy with coupled active surfaces , 2005, IEEE Transactions on Image Processing.

[31]  W. Huttner,et al.  Selective Lengthening of the Cell Cycle in the Neurogenic Subpopulation of Neural Progenitor Cells during Mouse Brain Development , 2005, The Journal of Neuroscience.

[32]  D. van der Kooy,et al.  p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. , 2005, Genes & development.

[33]  Philippe Van Ham,et al.  Tracking of migrating cells under phase-contrast video microscopy with combined mean-shift processes , 2005, IEEE Transactions on Medical Imaging.