Molecular architecture of lineage allocation and tissue organization in early mouse embryo
Guangdun Peng1,2,3,4,11,12*, Shengbao Suo5,10,11, Guizhong Cui1,11, Fang Yu1,11, Ran Wang1, Jun Chen1, Shirui Chen1, Zhiwen Liu1,
Guoyu Chen5, Yun Qian1, Patrick P. L. Tam6,7, Jing-Dong J. Han5,8,12* & Naihe Jing1,4,9,12*

During post-implantation development of the mouse embryo,
descendants of the inner cell mass in the early epiblast transit
from the naive to primed pluripotent state1. Concurrently, germ
layers are formed and cell lineages are specified, leading to the
establishment of the blueprint for embryogenesis. Fate-mapping
and lineage-analysis studies have revealed that cells in different
regions of the germ layers acquire location-specific cell fates
during gastrulation2–5. The regionalization of cell fates preceding
the formation of the basic body plan—the mechanisms of which
are instrumental for understanding embryonic programming and
stem-cell-based translational study—is conserved in vertebrate
embryos6–8. However, a genome-wide molecular annotation of
lineage segregation and tissue architecture of the post-implantation
embryo has yet to be undertaken. Here we report a spatially resolved
transcriptome of cell populations at defined positions in the germ
layers during development from pre- to late-gastrulation stages. This
spatiotemporal transcriptome provides high-resolution digitized
in situ gene-expression profiles, reveals the molecular genealogy of
tissue lineages and defines the continuum of pluripotency states in
time and space. The transcriptome further identifies the networks
of molecular determinants that drive lineage specification and tissue
patterning, supports a role of Hippo–Yap signalling in germ-layer
development and reveals the contribution of visceral endoderm to
the endoderm in the early mouse embryo.