The pluripotent state in mouse and human

Davidson, Kathryn; Mason, Elizabeth A.; Pera, Martín F.

doi:10.1242/dev.116061

Cited by 144 publications

(128 citation statements)

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“…More recently, naïve-state hESCs have been generated by toggling conventional hESCs back from the primed state (e.g., LIS1, WIN1, and H1-4iLIF lines) (3,(11)(12)(13) or by deriving new hESC lines from human six-to eight-cell embryos (e.g., ELF1 line) using naïve-state growth conditions (12). The molecular programs used to support naïve pluripotency in hESCs and the degree of conservation of the different states of pluripotency between human and mouse PSCs is an area of active investigation (14).…”

mentioning

confidence: 99%

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Robitaille

Berndt

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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111

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In both mice and humans, pluripotent stem cells (PSCs) exist in at least two distinct states of pluripotency, known as the naïve and primed states. Our understanding of the intrinsic and extrinsic factors that enable PSCs to self-renew and to transition between different pluripotent states is important for understanding early development. In mouse embryonic stem cells (mESCs), Wnt proteins stimulate mESC self-renewal and support the naïve state. In human embryonic stem cells (hESCs), Wnt/β-catenin signaling is active in naïve-state hESCs and is reduced or absent in primed-state hESCs. However, the role of Wnt/β-catenin signaling in naïve hESCs remains largely unknown. Here, we demonstrate that inhibition of the secretion of Wnts or inhibition of the stabilization of β-catenin in naïve hESCs reduces cell proliferation and colony formation. Moreover, we show that addition of recombinant Wnt3a partially rescues cell proliferation in naïve hESCs caused by inhibition of Wnt secretion. Notably, inhibition of Wnt/β-catenin signaling in naïve hESCs did not cause differentiation. Instead, it induced primed hESC-like proteomic and metabolic profiles. Thus, our results suggest that naïve hESCs secrete Wnts that activate autocrine or paracrine Wnt/β-catenin signaling to promote efficient self-renewal and inhibit the transition to the primed state.Wnt/β-catenin signaling | naïve pluripotency | naïve-to-primed transition | human embryonic stem cells | self-renewal

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mentioning

confidence: 99%

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Robitaille

Berndt

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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111

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“…Both totipotent as well as pluripotent cells belong to the germline, and both states require a finely tuned temporal and spatial control [1,2] . Interestingly, the molecular regulation of pluripotency and the signal transduction pathways associated with this developmental state are not fully conserved in different mammalian species as has been shown for pluripotent cells of human and mouse origin [3,4] . Recently, marmoset monkey and mouse pluripotent cells directly isolated from embryos were also compared [5] .…”

Section: The Totipotent and Pluripotent Stages Of The Germlinementioning

confidence: 99%

Characteristic Features of Male Germline Development in Primates

Behr¹

2017

Genetics of Human Infertility

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The germline is constituted by all cells that have the potential to transmit their genetic information to the next generation. The germline can be considered as a defined sequence of genetic, cellular, and developmental processes recurring in each generation in order to ensure the continuity of a species-specific reproduction program. Although basic mechanisms of germline development in mammals are highly conserved, relatively slight yet relevant modifications of germline development evolved in different groups of mammals to adapt the entire process to the specific requirements of and conditions in each species. This review highlights selected aspects that illustrate germline adaptations and characteristics in primates mainly in comparison to the mouse, which is the best investigated mammalian model organism in reproductive biology. The germline is constituted by all cells that have the potential to submit their genetic information to the next generation. The cycle of the germline in mammals is characterized by the recurring sequence of (1) fertilization, i.e., fusion of 2 haploid gametes, resulting in (2) a diploid phase of early embryonic development, which leads to (3) the specification and separation of germ cells (primordial germ cells; PGCs) from somatic cells, followed by (4) several rounds of mitotic divisions of the germ cells. Then (5) the germ cells enter meiosis, i.e., the genetic reduction division, resulting in (6) haploid cells forming gametes again. Fusion of the haploid male and the female gametes completes the cycle of the germline and begins the next generation ( Fig. 1 ). This sequence of events occurs in all mammals. However, different species exhibit specific adaptations and characteristics of 1 or more phases of the cycle of the germline. Remarkably, the cycle of the germline is an extremely robust process that works "endlessly". On the other hand, certain dynamics of the germline is essential for evolution since only modifications of the germline cells can lead to (genetically or epigenetically) inherited traits possibly resulting in better-adapted offspring and, hence, supporting species diversion. In light of these conflicting goals, namely germline stability and genome dynamics, some selected characteristic features of male germ cell development in pri- A new generation is initiated by the formation of a zygote, i.e., the fertilized oocyte. In the morula-stage embryo, the individual cells (blastomeres) are not yet specified. They are all potential progenitor cells of the prospective germ cells. The blastocyst consists of 2 clearly distinguishable cell populations: the inner cell mass cells (highlighted by red arrows) and the outer cell layer, i.e., the trophoblast. The germ cells develop from the inner cell mass cells. In the implantation embryo the first specified germ cells, called PGCs, occur. In the somite-stage embryos they are frequently located in the epithelium of the developing hind gut (red arrows). In the fetus, most PGCs have entered the forming gonad. The magnifie...

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“…In contrast to the wealth of information derived from mouse studies, we know relatively little about how embryonic pluripotency is regulated in humans (Davidson et al, 2015). In vitro fertilization provides an accessible way of studying pre-implantation human development until the blastocyst stage.…”

Section: Pluripotency In Vivomentioning

confidence: 99%

An overview of mammalian pluripotency

Yamauchi

Belmonte

2016

Development

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Mammalian pluripotency is the ability to give rise to all somatic cells as well as the germ cells of an adult mammal. It is a unique feature of embryonic epiblast cells, existing only transiently, as cells pass through early developmental stages. By contrast, pluripotency can be captured and stabilized indefinitely in cell culture and can also be reactivated in differentiated cells via nuclear reprogramming. Pluripotent stem cells (PSCs) are the in vitro carriers of pluripotency and they can inhabit discrete pluripotent states depending on the stage at which they were derived and their culture conditions. Here, and in the accompanying poster, we provide a summary of mammalian pluripotency both in vivo and in vitro, and highlight recent and future applications of PSCs for basic and translational research.

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The pluripotent state in mouse and human

Cited by 144 publications

References 71 publications

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Characteristic Features of Male Germline Development in Primates

An overview of mammalian pluripotency

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