Quantitative analyses for elucidating mechanisms of cell fate commitment in the mouse blastocyst

In recent years we have witnessed a shift from qualitative image analysis towards higher resolution, quantitative analyses of imaging data in developmental biology. This shift has been fueled by technological advances in both imaging and analysis software. We have recently developed a tool for accurate, semi-automated nuclear segmentation of imaging data from early mouse embryos and embryonic stem cells. We have applied this software to the study of the first lineage decisions that take place during mouse development and established analysis pipelines for both static and time-lapse imaging experiments. In this paper we summarize the conclusions from these studies to illustrate how quantitative, single-cell level analysis of imaging data can unveil biological processes that cannot be revealed by traditional qualitative studies.

[1]  J. Nichols,et al.  Nanog safeguards pluripotency and mediates germline development , 2007, Nature.

[2]  Philipp J. Keller,et al.  Fast, accurate reconstruction of cell lineages from large-scale fluorescence microscopy data , 2014, Nature Methods.

[3]  Minjung Kang,et al.  FGF4 is required for lineage restriction and salt-and-pepper distribution of primitive endoderm factors but not their initial expression in the mouse , 2013, Development.

[4]  Wolfgang Huber,et al.  Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages , 2013, Nature Cell Biology.

[5]  Takashi Hiiragi,et al.  Stochastic patterning in the mouse pre-implantation embryo , 2007, Development.

[6]  篠原 隆司,et al.  Induction of pluripotent stem cell cells from germ cells , 2012 .

[7]  A. Hadjantonakis,et al.  Cellular dynamics in the early mouse embryo: from axis formation to gastrulation. , 2010, Current opinion in genetics & development.

[8]  Anna-Katerina Hadjantonakis,et al.  The primitive endoderm lineage of the mouse blastocyst: sequential transcription factor activation and regulation of differentiation by Sox17. , 2011, Developmental biology.

[9]  A. Hadjantonakis,et al.  GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst. , 2014, Developmental cell.

[10]  R. Gardner Origin and differentiation of extraembryonic tissues in the mouse. , 1983, International review of experimental pathology.

[11]  Periklis Pantazis,et al.  Oct4 kinetics predict cell lineage patterning in the early mammalian embryo , 2011, Nature Cell Biology.

[12]  M. Murakami,et al.  The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells , 2003, Cell.

[13]  B. Płusa,et al.  Early cell fate decisions in the mouse embryo. , 2013, Reproduction.

[14]  Tony Pawson,et al.  Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. , 2006, Developmental cell.

[15]  Anna-Katerina Hadjantonakis,et al.  Anatomy of a blastocyst: Cell behaviors driving cell fate choice and morphogenesis in the early mouse embryo , 2013, Genesis.

[16]  A. Puliafito,et al.  Heterogeneities in Nanog Expression Drive Stable Commitment to Pluripotency in the Mouse Blastocyst. , 2015, Cell reports.

[17]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[18]  T P Fleming,et al.  A quantitative analysis of cell allocation to trophectoderm and inner cell mass in the mouse blastocyst. , 1987, Developmental biology.

[19]  Y. Yamanaka,et al.  FGF4 is a limiting factor controlling the proportions of primitive endoderm and epiblast in the ICM of the mouse blastocyst. , 2013, Developmental biology.

[20]  Shankar Srinivas,et al.  Limited predictive value of blastomere angle of division in trophectoderm and inner cell mass specification , 2014, Development.

[21]  C. Lim,et al.  Regulated Fluctuations in Nanog Expression Mediate Cell Fate Decisions in Embryonic Stem Cells , 2009, PLoS biology.

[22]  J. Nichols,et al.  Pluripotency in the embryo and in culture. , 2012, Cold Spring Harbor perspectives in biology.

[23]  Ullrich Köthe,et al.  Ilastik: Interactive learning and segmentation toolkit , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[24]  J. Rossant,et al.  Investigation of the fate of 4-5 day post-coitum mouse inner cell mass cells by blastocyst injection. , 1979, Journal of embryology and experimental morphology.

[25]  Minjung Kang,et al.  Stem Cell Reports , Volume 2 Supplemental Information A Rapid and Efficient 2 D / 3 D Nuclear Segmentation Method for Analysis of Early Mouse Embryo and Stem Cell Image Data , 2014 .

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

[27]  A. Hadjantonakis,et al.  Ex utero culture and live imaging of mouse embryos. , 2011, Methods in molecular biology.

[28]  Ge Guo,et al.  Nanog Is the Gateway to the Pluripotent Ground State , 2009, Cell.

[29]  J. Nichols,et al.  Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells , 2003, Cell.

[30]  R. Beddington,et al.  Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo , 1996, Current Biology.