| Summary: | In mammals, specification of the three major germ layers occurs during
gastrulation, when cells ingressing through the primitive streak differentiate
into the precursor cells of major organ systems. However, the molecular
mechanisms underlying this process remain unclear, as numbers of gastrulating
cells are very limited. In the E6.5 mouse embryo, cells located at the junction
between the extra-embryonic region and the epiblast on the posterior side of the
embryo undergo an epithelial-to-mesenchymal transition (EMT) and ingress through
the primitive streak (PS). Subsequently, cells migrate, either surrounding the
prospective ectoderm contributing to the embryo proper, or into the
extra-embryonic region to form the yolk sac (YS), umbilical cord and placenta.
Fate mapping has shown that mature tissues such as blood and heart originate
from specific regions of the pre-gastrula epiblast1 but the plasticity of cells within the embryo and the function of
key cell type-specific transcription factors remain unclear. Here we analyse
1,205 cells from the epiblast and nascent Flk1+ mesoderm of gastrulating mouse
embryos using single cell RNA-sequencing, representing the first
transcriptome-wide in vivo view of early mesoderm formation during mammalian
gastrulation. Additionally, using knock-out mice, we study the function of Tal1,
a key hematopoietic transcription factor (TF), and demonstrate, contrary to
previous studies performed using retrospective assays2,3, that
Tal1 knock out does not immediately bias precursor cells
towards a cardiac fate.
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