A5014695527- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Renal and related cancers
- Congenital heart defects research
- Animal Genetics and Reproduction
- Reproductive Biology and Fertility
- Developmental Biology and Gene Regulation
- Tissue Engineering and Regenerative Medicine
- Advanced Fluorescence Microscopy Techniques
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cell Image Analysis Techniques
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- bioluminescence and chemiluminescence research
- Pancreatic function and diabetes
- Viral Infectious Diseases and Gene Expression in Insects
Memorial Sloan Kettering Cancer Center
2016-2025
Cornell University
2005-2024
Kettering University
2011-2021
Wellcome/MRC Cambridge Stem Cell Institute
2020
Medical Research Council
2020
University of Cambridge
2020
Mount Sinai Hospital
2009
Icahn School of Medicine at Mount Sinai
2006
Columbia University
2000-2005
Zero to Three
2005
The trophoblast cell lineage is essential for the survival of mammalian embryo in utero. This specified before implantation into uterus and restricted to form fetal portion placenta. A culture mouse blastocysts or early postimplantation trophoblasts presence fibroblast growth factor 4 (FGF4) permitted isolation permanent stem lines. These lines differentiated other subtypes vitro absence FGF4 exclusively contributed vivo chimeras.
The first two lineages to differentiate from a pluripotent cell population during mammalian development are the extraembryonic trophectoderm (TE) and primitive endoderm (PrE). Whereas mechanisms of TE specification have been extensively studied, segregation PrE epiblast (EPI) has received comparatively little attention. A current model suggests precursors exhibit an apparently random distribution within inner mass early blastocyst then segregate their final position lining cavity by late...
Dorit B. Donoviel, Anna-Katerina Hadjantonakis, Masaki Ikeda, Hui Zheng, Peter St George Hyslop, and Alan Bernstein Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G-1X5; Centre for in Neurodegenerative Diseases Department of Medicine, Division Neurology, University Toronto. The Toronto M5S-3H2; Merck Laboratories, Rahway, New Jersey 07065 USA; Medical Genetics Microbiology, M5S-1A8
Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate normal morphogenetic processes, i.e. they pluripotent. However, although steered differentiate cell types organism, cannot organise themselves structures resemble embryos. When aggregated embryoid bodies develop disorganised masses different with little spatial coherence....
The prospective fate of cells in the primitive streak was examined at early, mid and late stages mouse gastrula development to determine order allocation mesoderm extraembryonic membranes fetal tissues. At early-streak stage, contribute predominantly tissues as previously found. However, a surprising observation is that erythropoietic precursors yolk sac emerge earlier than bulk vitelline endothelium, which formed continuously throughout development. This may suggest endothelial cell...
Abstract Background Understanding the dynamic cellular behaviors and underlying molecular mechanisms that drive morphogenesis is an ongoing challenge in biology. Live imaging provides necessary methodology to unravel synergistic stereotypical cell events shape embryo. Genetically-encoded reporters represent essential tool for live imaging. Reporter strains can be engineered by placing cis -regulatory elements of interest direct expression a desired reporter gene. In case canonical Wnt...
The emergence of pluripotent epiblast (EPI) and primitive endoderm (PrE) lineages within the inner cell mass (ICM) mouse blastocyst involves initial co-expression lineage-associated markers followed by mutual exclusion salt-and-pepper distribution lineage-biased cells. Precisely how EPI PrE fate commitment occurs is not entirely clear; however, previous studies in mice have implicated FGF/ERK signaling this process. Here, we investigated phenotype resulting from zygotic maternal/zygotic...
Abstract Molecular profiling of single cells has advanced our knowledge the molecular basis development. However, current approaches mostly rely on dissociating from tissues, thereby losing crucial spatial context regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes tissue sections mouse embryos at 8–12 somite stage. By integrating and multiplexed transcriptional...
During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of embryo. Similarly, human pluripotent stem (PSCs) undergo organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for human, we developed a mouse PSC micropattern system and, with direct comparisons to embryos, reveal robust distinct regional identities. BMP, WNT, ACTIVIN FGF directed epiblast-like an epithelial-to-mesenchymal transition...
A key challenge of analyzing data from high-resolution spatial profiling technologies is to suitably represent the features cellular neighborhoods or niches. Here we introduce covariance environment (COVET), a representation that leverages gene-gene covariate structure across cells in niche capture multivariate nature interactions within it. We define principled optimal transport-based distance metric between COVET niches scales millions cells. Using encode context, developed environmental...
Generation of inside cells that develop into inner cell mass (ICM) and outside trophectoderm is central to the development early mouse embryo. Critical this decision polarity associated asymmetric (differentiative) divisions 8-cell-stage blastomeres. The underlying molecular mechanisms for these events are not understood. As Par3/aPKC complex has a role in establishing cellular division orientation other systems, we explored its potential function developing We show both Par3 aPKC adopt...
Abstract Background Advances in optical imaging modalities and the continued evolution of genetically-encoded fluorescent proteins are coming together to facilitate study cell behavior at high resolution living organisms. As a result, using autofluorescent protein reporters is gaining popularity mouse transgenic targeted mutagenesis applications. Results We have used embryonic stem cell-mediated transgenesis label cells sub-cellular vivo , evaluate fusion human histone green for ubiquitous...
Non-invasive autofluorescent reporters have revolutionized lineage labeling in an array of different organisms. In recent years green fluorescent protein (GFP) from the bioluminescent jellyfish Aequoria Victoria has gained popularity mouse transgenic and gene targeting regimes 1. It offers several advantages over conventional gene-based reporters, such as lacZ alkaline phosphatase, that its visualization does not require a chromogenic substrate can be realized vivo. We previously...