scholarly journals Telomeric noncoding RNA promotes mouse embryonic stem cell self-renewal through inhibition of TCF3 activity

2018 ◽  
Vol 314 (6) ◽  
pp. C712-C720 ◽  
Author(s):  
Xiaojuan Xu ◽  
Mengmeng Guo ◽  
Na Zhang ◽  
Shoudong Ye
Keyword(s):  
Stem Cells ◽  
Noncoding Rna ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Promoting Effect ◽  
Self Renewal ◽  
Downstream Target ◽  
Undifferentiated State ◽  
Fate Decision

Although long noncoding RNAs (lncRNAs) are emerging as new modulators in the fate decision of pluripotent stem cells, the functions of specific lncRNAs remain unclear. Here, we found that telomeric RNA (TERRA or TelRNA), one type of lncRNAs, is highly expressed in mouse embryonic stem cells (mESCs) but declines significantly upon differentiation. TERRA is induced by the Wnt/β-catenin signaling pathway and can reproduce its self-renewal-promoting effect when overexpressed. Further studies revealed that T cell factor 3 ( TCF3) is a potential downstream target of TERRA and mediates the effect of TERRA in mESC maintenance. TERRA inhibits TCF3 transcription, while enforced TCF3 expression abrogates the undifferentiated state of mESCs supported by TERRA. Accordingly, the transcripts of the pluripotency genes Esrrb, Tfcp2l1, and Klf2, repressed by TCF3 in mESCs, are increased in TERRA-overexpressing cells. Our study therefore highlights the important role of TERRA in mESC maintenance and also uncovers a mechanism by which TERRA promotes self-renewal. These data will expand our understanding of the pluripotent regulatory network of ESCs.

scholarly journals Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Paulina A. Latos ◽  
Angela Goncalves ◽  
David Oxley ◽  
Hisham Mohammed ◽  
Ernest Turro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Es Cells ◽  
Embryonic Stem ◽  
Transcriptional Networks ◽  
Self Renewal ◽  
Downstream Target ◽  
Trophoblast Stem

Abstract Esrrb (oestrogen-related receptor beta) is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth factor (Fgf) signalling and is critical to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome using mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.

scholarly journals Dermatan-4-O-Sulfotransferase-1 Contributes to the Undifferentiated State of Mouse Embryonic Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chika Ogura ◽  
Shoko Nishihara
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Keratan Sulfate ◽  
Mouse Embryonic Stem Cells ◽  
Human Escs ◽  
Self Renewal ◽  
Human Neural Stem Cells ◽  
Undifferentiated State ◽  
Endodermal Differentiation

Mouse embryonic stem cells (mESCs) have the properties of self-renewal and pluripotency. Various signals and growth factors maintain their undifferentiated state and also regulate their differentiation. Glycosaminoglycans are present on the cell surface and in the cell matrix as proteoglycans. Previously, we and other groups reported that the glycosaminoglycan heparan sulfate contributes to both maintenance of undifferentiated state and regulation of mESC differentiation. It has been shown that chondroitin sulfate is needed for pluripotency and differentiation of mESCs, while keratan sulfate is a known marker of human ESCs or induced pluripotent stem cells. We also found that DS promotes neuronal differentiation from mESCs and human neural stem cells; however, the function of DS in the maintenance of mESCs has not yet been revealed. Here, we investigated the role of DS in mESCs by knockdown (KD) or overexpression (O/E) of the dermatan-4-O-sulfotransferase-1 (D4ST1) gene. We found that the activity of the ESC self-renewal marker alkaline phosphatase was reduced in D4ST1 KD mESCs, but, in contrast, increased in D4ST1 O/E mESCs. D4ST1 KD promoted endodermal differentiation, as indicated by an increase in Cdx2 expression. Conversely, Cdx2 expression was decreased by D4ST1 O/E. Wnt signaling, which is also involved in endodermal differentiation, was activated by D4ST1 KD and suppressed by D4ST1 O/E. Collectively, these results demonstrate that D4ST1 contributes to the undifferentiated state of mESCs. Our findings provide new insights into the function of DS in mESCs.

scholarly journals Resf1 supports embryonic stem cell self-renewal and effective germline entry

2021 ◽  
Author(s):  
Matus Vojtek ◽  
Ian Chambers
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Line ◽  
Primordial Germ Cell ◽  
Embryonic Stem ◽  
Cell Specification ◽  
Self Renewal ◽  
Downstream Target ◽  
Germ Cell Specification

Retroelement silencing factor 1 (Resf1) interacts with the key regulators of mouse embryonic stem cells (ESCs) Oct4 and Nanog, and its absence results in sterility of mice. However, the function of Resf1 in ESCs and germ line specification is poorly understood. In this study, we used Resf1 knockout cell lines to determine the requirements of RESF1 for ESCs self-renewal and for in vitro specification of ESCs into primordial germ cell-like cells (PGCLCs). We found that deletion of Resf1 in ESCs cultured in serum and LIF reduces self-renewal potential whereas episomal expression of RESF1 has a modest positive effect on ESC self-renewal. In addition, RESF1 is not required for the capacity of NANOG and its downstream target ESRRB to drive self-renewal in the absence of LIF. However, Resf1 deletion reduces efficiency of PGCLC differentiation in vitro. These results identify Resf1 as a novel player in the regulation of pluripotent stem cells and germ cell specification.

scholarly journals SALL4 and microRNA: The Role of Let-7

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1301
Author(s):  
Jun Liu ◽  
Madeline A. Sauer ◽  
Shaza Hussein ◽  
Junyu Yang ◽  
Daniel G. Tenen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem ◽  
Mammalian Development ◽  
Multiple Cancer ◽  
Self Renewal ◽  
Zinc Finger Transcription Factor ◽  
Different Types ◽  
Organ Specific ◽  
Cancer Types

SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene fam-ily. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regard-ing how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as im-portant regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize cur-rent knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.

New Proteomic Insights on the Role of NPR-A in Regulating Self-Renewal of Embryonic Stem Cells

2014 ◽  
Vol 10 (4) ◽  
pp. 561-572 ◽  
Author(s):  
Sameh Magdeldin ◽  
Tadashi Yamamoto ◽  
Ikuo Tooyama ◽  
Essam M. Abdelalim
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Self Renewal

scholarly journals The role of Ca2+ signaling on the self-renewal and neural differentiation of embryonic stem cells (ESCs)

Cell Calcium ◽  
2016 ◽  
Vol 59 (2-3) ◽  
pp. 67-74 ◽  
Author(s):  
Baixia Hao ◽  
Sarah E. Webb ◽  
Andrew L. Miller ◽  
Jianbo Yue
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Differentiation ◽  
Embryonic Stem ◽  
The Self ◽  
Self Renewal
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