There has been recent renewed interest in studying human early embryonic development. The advent of improved culture conditions to maintain blastocysts in vitro for an extended period and the ...emerging stem-cell-based models of the blastocyst and peri-implantation embryos have provided new information that is relevant to early human embryogenesis. However, the mechanism of lineage development and embryonic patterning, and the molecular pathways involved in their regulation, are still not well understood. Interest in human embryonic development has been reinvigorated recently given numerous technical advances. In this review, Rossant and Tam discuss new insights into human embryogenesis gathered from successes in culturing human embryos in vitro and stem-cell-based embryo models. Then they outline what questions still need answering.
We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched ...molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.
Pathways underlying mouse embryonic development have always informed efforts to derive, maintain, and drive differentiation of human pluripotent stem cells. However, direct application of mouse ...embryology to the human system has not always been successful because of fundamental developmental differences between species. The naive pluripotent state of mouse embryonic stem cells (ESCs), in particular, has been difficult to capture in human ESCs, and appears to be transitory in the human embryo itself. Further studies of human and non-human primate embryo development are needed to untangle the complexities of pluripotency networks across mammalian species.
Direct comparisons between events of pre- and peri-implantation development in the human, as well as in non-human primates, and the mouse have highlighted numerous similarities and differences. Rossant and Tam summarize those findings and discuss their relevance to derivation of human pluripotent stem cells and their differentiation in vitro.
During early mammalian development, as the pluripotent cells that give rise to all of the tissues of the body proliferate and expand in number, they pass through transition states marked by a ...stepwise restriction in developmental potential and by changes in the expression of key regulatory genes. Recent findings show that cultured stem-cell lines derived from different stages of mouse development can mimic these transition states. They further reveal that there is a high degree of heterogeneity and plasticity in pluripotent populations in vitro and that these properties are modulated by extrinsic signalling. Understanding the extrinsic control of plasticity will guide efforts to use human pluripotent stem cells in research and therapy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The investigation into lineage allocation and early asymmetries in the pre- and peri-implantation mouse embryo is gaining momentum. As we review here, new insights have been gained into the cellular ...and molecular events that lead to the establishment of the three lineages of the blastocyst, to the determination of the origin and the fates of the visceral endoderm in the peri-implantation mouse embryo, and to the generation of cellular and molecular activities that accompany the emergence of asymmetries in the pre-gastrulation embryo. We also discuss the continuing debate that surrounds the relative impacts of early lineage bias versus the stochastic allocation of cells with respect to the events that pattern the blastocyst and initiate its later asymmetries.
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 state
. 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 gastrulation
. 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 embryos
. 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.
During early mouse embryogenesis, temporal and spatial regulation of gene expression and cell signalling influences lineage specification, embryonic polarity, the patterning of tissue progenitors and ...the morphogenetic movement of cells and tissues. Uniquely in mammals, the extraembryonic tissues are the source of signals for lineage specification and tissue patterning. Here we discuss recent discoveries about the lead up to gastrulation, including early manifestations of asymmetry, coordination of cell and tissue movements and the interactions of transcription factors and signalling activity for lineage allocation and germ-layer specification.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
8.
Exploring early human embryo development Rossant, Janet; Tam, Patrick P L
Science (American Association for the Advancement of Science),
2018-Jun-08, 2018-06-08, 20180608, Letnik:
360, Številka:
6393
Journal Article
Recenzirano
Stem cell–derived models enable understanding of human embryogenesis
Human in vitro fertilization (IVF) has been around for 40 years and yet we still do not fully understand how to ensure the ...generation of healthy embryos and to prevent unwanted genetic or epigenetic changes that may arise during in vitro culture. Once the embryo is transferred to the uterus to continue gestation, early implantation and the initial phases of embryogenesis and placenta formation are hidden from easy access for research. Errors in early development may lead to implantation problems, fetal defects, and placental insufficiencies, resulting in early pregnancy loss. Studying mice has provided clues about the major genetic and epigenetic events of early embryo development but, as is becoming increasingly evident, there are morphological and genetic differences between mice and humans that make cross-species comparisons problematic (
1
). Recent experimental approaches working directly with human embryos, or with embryo-derived stem cells and nonhuman primate embryos, have opened new avenues for studying the development of early human embryos.
Mouse epiblast stem cells (EpiSCs) can be derived from a wide range of developmental stages. To characterize and compare EpiSCs with different origins, we derived a series of EpiSC lines from ...pregastrula stage to late-bud-stage mouse embryos. We found that the transcriptomes of these cells are hierarchically distinct from those of the embryonic stem cells, induced pluripotent stem cells (iPSCs), and epiblast/ectoderm. The EpiSCs display globally similar gene expression profiles irrespective of the original developmental stage of the source tissue. They are developmentally similar to the ectoderm of the late-gastrula-stage embryo and behave like anterior primitive streak cells when differentiated in vitro and in vivo. The EpiSC lines that we derived can also be categorized based on a correlation between gene expression signature and predisposition to differentiate into particular germ-layer derivatives. Our findings therefore highlight distinct identifying characteristics of EpiSCs and provide a foundation for further examination of EpiSC properties and potential.
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•EpiSCs derived from different embryonic stages show similar molecular characteristics•EpiSCs are developmentally similar to late-gastrula-stage ectoderm•Differentiation features anterior primitive streak properties in vitro and in vivo•Germ-layer predisposition of EpiSCs correlates with gene expression
Mouse EpiSCs derived from a range of embryonic stages all resemble the anterior primitive streak but vary in germ-layer differentiation propensity in line with their specific gene expression profile.
Mouse embryonic stem cells derived from the epiblast contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and ...the primitive endoderm upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.
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