Dynamic stem cell states: naive to primed pluripotency in rodents and humans

Weinberger, Leehee; Ayyash, Muneef; Novershtern, Noa; Hanna, Jacob

doi:10.1038/nrm.2015.28

Cited by 515 publications

(463 citation statements)

References 121 publications

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“…This is possibly due to the different pluripotent states of hESC and mESCs, with mESCs being in a more naïve state (42). TBX3 overexpression cell culture models showed that it could promote hESC proliferation by repressing p14ARF and NFκBIB, an inhibitor of the NF-kappaB (NF-κB) pathway (41).…”

Section: Tbx3 In Development and In Stem Cell Biologymentioning

confidence: 99%

The T-Box transcription factor 3 in development and cancer

Willmer

Cooper

Peres

et al. 2017

BST

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Section: Tbx3 In Development and In Stem Cell Biologymentioning

confidence: 99%

The T-Box transcription factor 3 in development and cancer

Willmer

Cooper

Peres

et al. 2017

BST

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“…For example, one critical variable impacting the functional pluripotency of conventional hPSCs is their developmental, molecular and epigenetic commonality with ʻprimed' mouse post-implantation epiblast stem cells (mEpiSCs) (Tesar et al, 2007;Brons et al, 2007;Chou et al, 2008;Kojima et al, 2014;Weinberger et al, 2016), which possess a less primitive pluripotency than inner cell mass (ICM)-derived mouse ESC (mESCs). For example, mEpiSCs cannot fully contribute to a blastocyst chimera and are resistant to chemical reversion to ICM-like naïve ʻground state' pluripotency with 'LIF-2i' (MEK/ERK and GSK3β signal inhibition) (Bernemann et al, 2011;Ying et al, 2008;Marks et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Tankyrase inhibition promotes a stable human naïve pluripotent state with improved functionality

et al. 2016

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The derivation and maintenance of human pluripotent stem cells (hPSCs) in stable naïve pluripotent states has a wide impact in human developmental biology. However, hPSCs are unstable in classical naïve mouse embryonic stem cell (ESC) WNT and MEK/ERK signal inhibition (2i) culture. We show that a broad repertoire of conventional hESC and transgene-independent human induced pluripotent stem cell (hiPSC) lines could be reverted to stable human preimplantation inner cell mass (ICM)-like naïve states with only WNT, MEK/ERK, and tankyrase inhibition (LIF-3i). LIF-3i-reverted hPSCs retained normal karyotypes and genomic imprints, and attained defining mouse ESC-like functional features, including high clonal self-renewal, independence from MEK/ERK signaling, dependence on JAK/ STAT3 and BMP4 signaling, and naïve-specific transcriptional and epigenetic configurations. Tankyrase inhibition promoted a stable acquisition of a human preimplantation ICM-like ground state via modulation of WNT signaling, and was most efficacious in efficiently reprogrammed conventional hiPSCs. Importantly, naïve reversion of a broad repertoire of conventional hiPSCs reduced lineage-primed gene expression and significantly improved their multilineage differentiation capacities. Stable naïve hPSCs with reduced genetic variability and improved functional pluripotency will have great utility in regenerative medicine and human disease modeling.

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“…The robust spermatogonial stem cell culture in mice may reflect the more primitive developmental state of the mouse spermatogonial stem cells compared to the primate counterparts. In this context, it is tempting to speculate that the recently established concept of a naïve and a primed state of pluripotent stem cells [86] can also be translated to mouse (naïve) and primate (primed) spermatogonial stem cells.…”

Section: Spermatogonial Stem Cell Culturementioning

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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Dynamic stem cell states: naive to primed pluripotency in rodents and humans

Cited by 515 publications

References 121 publications

The T-Box transcription factor 3 in development and cancer

The T-Box transcription factor 3 in development and cancer

Tankyrase inhibition promotes a stable human naïve pluripotent state with improved functionality

Characteristic Features of Male Germline Development in Primates

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