CNOT3-Dependent mRNA Deadenylation Safeguards the Pluripotent State

Zheng, Xiaofeng; Yang, Pengyi; Lackford, Brad; Bennett, Brian D.; Wang, Li; Li, Hui; Wang, Yu; Miao, Yi‐Liang; Foley, Julie F.; Fargo, David C.; Jin, Ying; Williams, Carmen J.; Jothi, Raja; Hu, Guang

doi:10.1016/j.stemcr.2016.09.007

Cited by 32 publications

(27 citation statements)

References 55 publications

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“…The CCR4-NOT complex promotes the decay of mRNAs that are relevant to immature tissue state, cell death, and proliferation to ensure differentiation or normal tissue development 16,24,55 . In contrast, the CCR4-NOT complex decreases mRNAs responsible for differentiation to maintain pluripotency [64][65][66] . Therefore, the CCR4-NOT complex contributes to proper mRNA expression by decreasing unnecessary mRNAs depending on the context.…”

Section: Cnot3βkomentioning

confidence: 99%

Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation

et al. 2020

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Pancreatic β-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Defects in β-cell function lead to hyperglycemia and diabetes mellitus. Here, we show that CNOT3, a CCR4-NOT deadenylase complex subunit, is dysregulated in islets in diabetic db/db mice, and that it is essential for murine β cell maturation and identity. Mice with β cell-specific Cnot3 deletion (Cnot3βKO) exhibit impaired glucose tolerance, decreased β cell mass, and they gradually develop diabetes. Cnot3βKO islets display decreased expression of key regulators of β cell maturation and function. Moreover, they show an increase of progenitor cell markers, β cell-disallowed genes, and genes relevant to altered β cell function. Cnot3βKO islets exhibit altered deadenylation and increased mRNA stability, partly accounting for the increased expression of those genes. Together, these data reveal that CNOT3-mediated mRNA deadenylation and decay constitute previously unsuspected post-transcriptional mechanisms essential for β cell identity.

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Section: Cnot3βkomentioning

confidence: 99%

Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation

et al. 2020

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“…At the blastocyst stage, Cited1 was expressed with a higher level in TE cells than in ICM cells. As controls, Cdx2 was found in the nucleus of TE cells in blastocysts, while Oct4 and Cnot3 (a known cytoplasmic protein) 41 were mainly detected in the nucleus and cytoplasm of ICM cells, respectively (Fig. 1i and S2B ).…”

Section: Resultsmentioning

confidence: 90%

“…Mouse embryo collection and immunofluorescence were carried out as described previously 8 , 41 . Briefly, pre-implantation embryos were flushed out from the oviducts or uterus of pregnant female mice and were subsequently fixed in 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

“…Immunofluorescence staining was performed using primary antibodies against Cdx2 (Biogenex, MU392A-UC), Oct4 (Santa Cruz, sc-101534) or Cited1 (Genetex, GTX114559), following standard protocols for whole embryo staining 8 . Image data were acquired with a Zeiss LSM 780 microscope 41 . The cell immunofluorescence staining was performed with following steps: ESCs on coverslips were firstly fixed with 4% paraformaldehyde for 15 min, permeabilized with 0.2 % Triton X-100 for 10 min, and blocked with 3% bovine serum albumin (BSA) for 30 min.…”

Section: Methodsmentioning

confidence: 99%

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Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling

Xü¹,

Luo

Fang³

et al. 2018

Cell Death Dis

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Trophoblast lineages, precursors of the placenta, are essential for post-implantation embryo survival. However, the regulatory network of trophoblast development remains incompletely understood. Here, we report that Cited1, a transcription coactivator, is a robust inducer for trophoblast-like state from mouse embryonic stem cells (ESCs). Depletion of Cited1 in ESCs compromises the trophoblast lineage specification induced by BMP signaling. In contrast, overexpression of Cited1 in ESCs induces a trophoblast-like state with elevated expression of trophoblast marker genes in vitro and generation of trophoblastic tumors in vivo. Furthermore, global transcriptome profile analysis indicates that ectopic Cited1 activates a trophoblast-like transcriptional program in ESCs. Mechanistically, Cited1 interacts with Bmpr2 and Smad4 to activate the Cited1–Bmpr2–Smad1/5/8 axis in the cytoplasm and Cited1–Smad4–p300 complexes in the nucleus, respectively. Collectively, our results show that Cited1 plays an important role in regulating trophoblast lineage specification through activating the BMP signaling pathway.

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“…In addition to the above mentioned epigenetic determinants and other regulatory components of transcription [2,8,9] and post-transcription [10,11], the components of translation might also influence restricted differentiation of iPSCs. Multiple studies conducted in cell-types ranging from bacteria to malignant cells indicate the existence of ribosomal subpopulations that differ in their protein complement cause diverse functional translational machinery [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Polymorphic dynamics of ribosomal proteins gene expression during somatic cell reprogramming and their differentiation in to specialized cells-types

Guthikonda

Bharathan

Rayabaram

et al. 2017

Preprint

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Factor induced pluripotent stem cells (iPSCs) offer great promise in regenerative medicine. However, accumulating evidence suggests that iPSCs are heterogeneous in comparison with embryonic stem cells (ESCs), and that is attributed to various genetic and epigenetic states of donor cells. In the light of the discovery of cell-type specialized ribosomal protein composition, its role as the cells transit through different stages of reprogramming and when iPSCs differentiate into specialized cell-types has not been explored to understand its influence in the reprogramming and differentiation process and outcome. By re-analyzing the publicly available gene expression datasets among ESCs, various sources of iPSCs and somatic cells and by studying the ribosomal protein gene expression during different stages of reprogramming of somatic cells and different passages of established iPSCs we found distinct patterns of their expression across multiple cell-types. We experimentally validated these results on the cells undergoing reprogramming from human dermal fibroblasts. Finally, by comparing publicly available data from iPSCs, iPSCs derived specialized cells and it’s in vivo counterparts, we show alterations in ribosomal gene expression during differentiation of specialized cells from iPSCs which may have Implications in the context of ribosomopathies. Our results provide an informatics framework for researchers in efficient generation of iPSCs that are equivalent to ESCs.

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CNOT3-Dependent mRNA Deadenylation Safeguards the Pluripotent State

Cited by 32 publications

References 55 publications

Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation

Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation

Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling

Polymorphic dynamics of ribosomal proteins gene expression during somatic cell reprogramming and their differentiation in to specialized cells-types

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