States and Origins of Mammalian Embryonic Pluripotency In Vivo and in a Dish

Ramos‐Ibeas, Priscila; Nichols, Jennifer; Alberio, Ramiro

doi:10.1016/bs.ctdb.2017.11.002

Cited by 10 publications

(5 citation statements)

References 142 publications

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“…In vitro evidences show that the requirements for trophectoderm and hypoblast development are less restrictive than those required for epiblast survival. Primary bovine trophectoderm cell cultures can be established using relatively simple media supplemented with 10 % serum ( 78 , 79 ), whereas conditions required for truly pluripotent epiblast cell culture in farm animals remain to be captured ( 80 ). In the same line, early in vitro culture systems designed for the development of post-hatching ungulate embryos were successful in achieving trophectoderm proliferation and some degree of hypoblast migration, but the epiblast degenerated ( 81 – 83 ).…”

Section: Epiblast Development Constitutes the Major Obstacle For Embryo Survivalmentioning

confidence: 99%

Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates

et al. 2021

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Embryonic losses constitute a major burden for reproductive efficiency of farm animals. Pregnancy losses in ungulate species, which include cattle, pigs, sheep and goats, majorly occur during the second week of gestation, when the embryo experiences a series of cell differentiation, proliferation, and migration processes encompassed under the term conceptus elongation. Conceptus elongation takes place following blastocyst hatching and involves a massive proliferation of the extraembryonic membranes trophoblast and hypoblast, and the formation of flat embryonic disc derived from the epiblast, which ultimately gastrulates generating the three germ layers. This process occurs prior to implantation and it is exclusive from ungulates, as embryos from other mammalian species such as rodents or humans implant right after hatching. The critical differences in embryo development between ungulates and mice, the most studied mammalian model, have precluded the identification of the genes governing lineage differentiation in livestock species. Furthermore, conceptus elongation has not been recapitulated in vitro, hindering the study of these cellular events. Luckily, recent advances on transcriptomics, genome modification and post-hatching in vitro culture are shedding light into this largely unknown developmental window, uncovering possible molecular markers to determine embryo quality. In this review, we summarize the events occurring during ungulate pre-implantation development, highlighting recent findings which reveal that several dogmas in Developmental Biology established by knock-out murine models do not hold true for other mammals, including humans and farm animals. The developmental failures associated to in vitro produced embryos in farm animals are also discussed together with Developmental Biology tools to assess embryo quality, including molecular markers to assess proper lineage commitment and a post-hatching in vitro culture system able to directly determine developmental potential circumventing the need of experimental animals.

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Section: Epiblast Development Constitutes the Major Obstacle For Embryo Survivalmentioning

confidence: 99%

Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates

et al. 2021

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“…Moreover ERK inhibition in combination with WNT signalling stimulation was reported to prevent hypoblast segregation in mouse embryos and facilitates embryonic stem cell derivation [12]. However, this approach does not eliminate all hypoblast cells in bovine blastocysts, similar to observations in human and pig embryos, suggesting that other signals may regulate hypoblast segregation [5, 9–11, 13]. In view of these differences among mammals, a better understanding of early gene expression is needed.…”

Section: Introductionmentioning

confidence: 99%

A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos

et al. 2019

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Background The segregation of the hypoblast and the emergence of the pluripotent epiblast mark the final stages of blastocyst formation in mammalian embryos. In bovine embryos the formation of the hypoblast has been partially studied, and evidence shows that MEK signalling plays a limited role in the segregation of this lineage. Here we explored the role of different signalling pathways during lineage segregation in the bovine embryo using immunofluorescence analysis of NANOG and SOX17 as readouts of epiblast and hypoblast, respectively. Results We show that SOX17 starts to be expressed in 16–32-cell stage embryos, whereas NANOG is first detected from 8-cell stage. SOX17 is first co-expressed with NANOG, but these markers become mutually exclusive by the late blastocyst stage. By assessing the expression kinetics of NANOG/SOX17 we show that inhibition of MEK signalling can eliminate SOX17 expression in bovine blastocysts, without altering NANOG expression. Modulation of WNT, PKC and LIF did not affect NANOG expression in the epiblast when used in combination with the ERK inhibitor. Conclusions This study shows that SOX17 can be used as a reliable early marker of hypoblast in the bovine, and based on its expression profile we show that the hypoblast segregates in day 7 blastocysts. Furthermore, SOX17 expression is abolished using 1 μM of PD0325901, without affecting the NANOG population in the epiblast. Modulation of WNT, PKC and LIF are not sufficient to support enhanced NANOG expression in the epiblast when combined with ERK inhibitor, indicating that additional signalling pathways should be examined to determine their potential roles in epiblast expansion. Electronic supplementary material The online version of this article (10.1186/s12861-019-0193-9) contains supplementary material, which is available to authorized users.

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“…Our understanding of the regulation of pluripotent stem cell self-renewal and lineage specification is in turn built largely on embryological paradigms, with developmental roadmaps providing critical knowledge of the key transitional stages, and pinpointing the extrinsic and internal molecular pathways drive cell fate decisions. In the mouse, we now have a fairly clear understanding of the states of pluripotency that span the developmental stages between the blastocyst and the late gastrula in vivo 1 . The characterization of mouse naive embryonic stem cells (ESC) and epiblast stem cells (EpiSC) 3,4 as in vitro equivalents of the preimplantation epiblast and the anterior primitive streak, respectively 5 , has shed considerable light on the properties of the cultured cells.…”

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Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal

et al. 2020

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Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation stage of embryogenesis. Heterogeneity within hPSC cultures complicates this interspecies comparison. Here we show that a subpopulation of archetypal hPSC enriched for high self-renewal capacity (ESR) has distinct properties relative to the bulk of the population, including a cell cycle with a very low G1 fraction and a metabolomic profile that reflects a combination of oxidative phosphorylation and glycolysis. ESR cells are pluripotent and capable of differentiation into primordial germ cell-like cells. Global DNA methylation levels in the ESR subpopulation are lower than those in mouse epiblast stem cells. Chromatin accessibility analysis revealed a unique set of open chromatin sites in ESR cells. RNA-seq at the subpopulation and single cell levels shows that, unlike mouse epiblast stem cells, the ESR subset of hPSC displays no lineage priming, and that it can be clearly distinguished from gastrulating and extraembryonic cell populations in the primate embryo. ESR hPSC correspond to an earlier stage of post-implantation development than mouse epiblast stem cells.

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States and Origins of Mammalian Embryonic Pluripotency In Vivo and in a Dish

Cited by 10 publications

References 142 publications

Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates

Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates

A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos

Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal

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