Building Pluripotency Identity in the Early Embryo and Derived Stem Cells

Rebuzzini, Paola; Zuccotti, Maurizio; Garagna, Silvia

doi:10.3390/cells10082049

Cited by 10 publications

(9 citation statements)

References 301 publications

(416 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…Besides cell shape, cell position, intercellular interaction and communication, blastomeres within each embryo have their own cellular properties and molecular signature (Rebuzzini et al, 2021). Maternal factors deposited in oocytes participate in the chromatin remodelling and genome reprogramming, to gradually activate the transcription of zygotes (Sha et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Single‐cell RNA sequencing reveals blastomere heterogeneity of 2‐cell embryos in pigs

Fang

Wang

Zhang

et al. 2023

Reprod Domestic Animals

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In mammals, single blastomeres from as early as 2‐cell embryos demonstrate heterogeneous developmental capacity and fate decision into different cell lineages. However, mechanisms underlying blastomere heterogeneity of 2‐cell embryos remain largely unresolved. Here, we analysed the molecular heterogeneity of full‐length mRNAs and their 3′UTR regions, based on the single‐cell RNA‐seq data of pig 2‐cell embryos generated from in vivo fertilization (in vivo), in vitro fertilization (in vitro) and parthenogenetic activation (PA), respectively. First, unsupervised clustering helped discover two different groups of blastomeres for 2‐cell pig embryos. Between these two groups of blastomeres in pig 2‐cell embryos, 35, 301 and 428 full‐length mRNAs respectively in in vivo, in vitro and PA embryo types were identified to be differentially expressed (padj ≤ .05 and |log2[fold change]| ≥1) (DE mRNAs), while 92, 89 and 42 mRNAs were shown to be with significantly different 3′UTR lengths (3′UTR DE) (padj ≤ .05). Gene enrichment for both DE mRNAs and 3′UTR DE mRNAs found multiple signalling pathways, including cell cycle, RNA processing. Few numbers of common DE mRNAs and 3′UTR DE mRNAs existed between in vitro and in vivo blastomeres derived from 2‐cell embryos, indicating the larger differences between in vitro and in vivo fertilized embryos. Integrative genomics viewer analysis further identified that 3′UTRs of HSDL2 and SGTA (in vivo), FAM204A and phosphoserine phosphatase (in vitro), PRPF40A and RPIA (PA) had >100 nt average length changes. Moreover, numbers and locations of regulatory elements (polyadenylation site, cytoplasmic polyadenylation element and microRNA binding sites) within 3′UTRs of these DE mRNAs were predicted. These results indicate that molecular heterogeneity existed among blastomeres from different types of pig 2‐cell embryos, providing useful information and novel insights into future functional investigation on its relationship with the subsequent embryo development and differentiation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals blastomere heterogeneity of 2‐cell embryos in pigs

Fang

Wang

Zhang

et al. 2023

Reprod Domestic Animals

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“…However, both the totipotent and pluripotent states of cells are dynamic, and the range of differentiation potential changes gradually with the progressive maturation of stem cells 15 . Furthermore, whereas totipotent stem cells are characterized by their homogenous proliferation, human pluripotent stem cells (hPSCs) gradually show cellular diversity in the ICM of a blastocyst 16 , 17 . The pluripotency of stem cells is thus limited, leading to the generation of three heterogeneous germ populations through pattern and structural formation events and gastrulation 18 .…”

Section: Introductionmentioning

confidence: 99%

New insights into the epitranscriptomic control of pluripotent stem cell fate

2022

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Each cell in the human body has a distinguishable fate. Pluripotent stem cells are challenged with a myriad of lineage differentiation options. Defects are more likely to be fatal to stem cells than to somatic cells due to the broad impact of the former on early development. Hence, a detailed understanding of the mechanisms that determine the fate of stem cells is needed. The mechanisms by which human pluripotent stem cells, although not fully equipped with complex chromatin structures or epigenetic regulatory mechanisms, accurately control gene expression and are important to the stem cell field. In this review, we examine the events driving pluripotent stem cell fate and the underlying changes in gene expression during early development. In addition, we highlight the role played by the epitranscriptome in the regulation of gene expression that is necessary for each fate-related event.

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“…This broad area of research aimed at a better characterization of the early developmental steps that could be further used to model various cell types and organ differentiation for cell therapies. The pluripotent cells emerging from this pre-implantation blastocyst represent a naïve pluripotent state with epigenetic, metabolic and transcriptomic features resembling the preimplantation blastocyst [ 3 , 4 , 5 ]. However, pluripotency has been considered as a continuum, including the primed pluripotency resembling the post-implantation epiblast [ 6 , 7 ], the formative state [ 8 ], in between or even alternative states such as the poised state [ 9 ] or the paused pluripotent state mimicking embryonic diapause [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Succinate as a New Actor in Pluripotency and Early Development?

Detraux

Renard

2022

Metabolites

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Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several intermediate states have been reported, as well as a small subpopulation of cells that have reacquired features of the 2C-embryo (2C-like cells) in naïve mouse ESC culture. Altogether, these represent a continuum of distinct pluripotency stages, characterized by metabolic transitions, for which we propose a new role for a long-known metabolite: succinate. Mostly seen as the metabolite of the TCA, succinate is also at the crossroad of several mitochondrial biochemical pathways. Its role also extends far beyond the mitochondrion, as it can be secreted, modify proteins by lysine succinylation and inhibit the activity of alpha-ketoglutarate-dependent dioxygenases, such as prolyl hydroxylase (PHDs) or histone and DNA demethylases. When released in the extracellular compartment, succinate can trigger several key transduction pathways after binding to SUCNR1, a G-Protein Coupled Receptor. In this review, we highlight the different intra- and extracellular roles that succinate might play in the fields of early pluripotency and embryo development.

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Building Pluripotency Identity in the Early Embryo and Derived Stem Cells

Cited by 10 publications

References 301 publications

Single‐cell RNA sequencing reveals blastomere heterogeneity of 2‐cell embryos in pigs

Single‐cell RNA sequencing reveals blastomere heterogeneity of 2‐cell embryos in pigs

New insights into the epitranscriptomic control of pluripotent stem cell fate

Succinate as a New Actor in Pluripotency and Early Development?

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