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The Blueprint of Mouse Development: Regionalization of Cell Fates and Spatial Transcriptome

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Plenary Lecture

The Blueprint of Mouse Development: Regionalization of Cell Fates and Spatial Transcriptome

Professor Patrick P L Tam, University of Sydney, Australia

Summary:

Gastrulation is a critical milestone of early mouse embryogenesis at which the primary germ layers are formed and the multipotent embryonic cells are allocated to the progenitors of tissue lineages within the germ layers. Fate mapping of the mouse embryo has revealed a distinctive regionalization of cell fates in the germ layers before gastrulation is completed, and lineage tracing studies showed that, concurrent with the formation of primary germ layer, the differentiation potency of embryonic cells is progressively restricted, culminating in the generation of lineage-restricted progenitors for specific tissue types. While snapshots of the expression of a selected set of genes may inform us of the signalling activity, tissue patterning and acquisition of specific cell fates, whole transcriptome of the embryo may provide a deeper insight into the genetic activity that underpins the developmental transition through gastrulation. To investigate the genetic activity that mediates the regionalization of cells fate and the organization of the body plan during the transition from cellular pluripotency to the restriction of lineage potency, we performed a high-resolution RNA-seq analysis on single mid-gastrulation mouse embryos to collate a spatial transcriptome of cell populations at defined locations in the epiblast. An important attribute of the spatial transcriptome when analysed in correlation with the regionalization of cell fates in the embryo is the delineation of region-specific transcriptional activity in the epiblast, which  provides the molecular annotation of the process of germ layer specification and a first glimpse of the genome activity in lineage specification and differentiation.

 

Biography of Professor Patrick Tam, PhD, FAA, FAHMS, FRSB, FRS

Patrick Tam

 

Professor Patrick Tam is the Deputy Director and Head of the Embryology Research Unit at the Children's Medical Research Institute, Senior Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC), Professor in the School of Medical Sciences, Sydney Medical School at University of Sydney and the Mok Hing-Yiu Distinguished Visiting Professor in the School of Biomedical Sciences of University of Hong Kong. 

Patrick Tam's research focuses on the systems-based investigation of the gene regulatory network underpinning the cellular and molecular mechanisms of body patterning during mouse development and the biology of embryo-derived stem cells. He pioneered the application of micromanipulation and embryo culture for analyzing mouse embryos and examining the development of the head and embryonic gut. The embryological analysis undertaken by his team at CMRI has enabled the construction of a series of fate-maps revealing the organization of the basic body plan of the early embryo.  The in-depth knowledge of cell differentiation during early embryogenesis laid the foundation for elucidating the genome activity that drive cell lineage development and directing the differentiation of stem cells into clinically useful cell types for therapy in regenerative medicine.

Patrick Tam is an Editor of Development and member of the editorial board of journals of developmental biology including Developmental Biology, Developmental Cell, Developmental Dynamics, Differentiation and Genesis.  He was a Guest Editor of BioEssays and Current Opinion of Genetics and Development and co-edited with James Nelson and Janet Rossant, a special issue of CSH Perspectives in Biology and the accompanying book on “Mammalian Development”. He serves on the scientific advisory board / council of Stem Cell Australia, RIKEN Centre for Developmental Biology, Max Planck Institute for Molecular Genetics, Eskitis Institute for Drug Discovery and the HKU School of Biomedical Sciences, and is currently a member of the Embryo Research Licensing Committee of the NHMRC.  In recognition of his professional accomplishment, he was awarded the President’s Medal of the Australia and New Zealand Society of Cell and Developmental Biology, and elected to the Fellowship of the Institute of Biology, the Australian Academy of Sciences, the Australian Academy of Health and Medical Sciences, the Royal Society of Biology and the Royal Society of London.