scholarly journals O-GlcNAcylation regulates the methionine cycle to promote pluripotency of stem cells

2020 ◽  
Vol 117 (14) ◽  
pp. 7755-7763
Author(s):  
Qiang Zhu ◽  
Xuejun Cheng ◽  
Yaxian Cheng ◽  
Junchen Chen ◽  
Huan Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Critical Role ◽  
Embryonic Stem ◽  
Methionine Metabolism ◽  
Somatic Cell Reprogramming ◽  
Methionine Cycle ◽  
Induced Pluripotent ◽  
Important Enzyme

Methionine metabolism is critical for the maintenance of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) pluripotency. However, little is known about the regulation of the methionine cycle to sustain ESC pluripotency. Here, we show that adenosylhomocysteinase (AHCY), an important enzyme in the methionine cycle, is critical for the maintenance and differentiation of mouse embryonic stem cells (mESCs). We show that mESCs exhibit high levels of methionine metabolism, whereas decreasing methionine metabolism via depletion of AHCY promotes mESCs to differentiate into the three germ layers. AHCY is posttranslationally modified with an O-linked β-N-acetylglucosamine sugar (O-GlcNAcylation), which is rapidly removed upon differentiation. O-GlcNAcylation of threonine 136 on AHCY increases its activity and is important for the maintenance of trimethylation of histone H3 lysine 4 (H3K4me3) to sustain mESC pluripotency. Blocking glycosylation of AHCY decreases the ratio of S-adenosylmethionine versus S-adenosylhomocysteine (SAM/SAH), reduces the level of H3K4me3, and poises mESC for differentiation. In addition, blocking glycosylation of AHCY reduces somatic cell reprogramming. Thus, our findings reveal a critical role of AHCY and a mechanistic understanding of O-glycosylation in regulating ESC pluripotency and differentiation.

A PRC2-Dependent Repressive Role of PRDM14 in Human Embryonic Stem Cells and Induced Pluripotent Stem Cell Reprogramming

Stem Cells ◽  
2013 ◽  
Vol 31 (4) ◽  
pp. 682-692 ◽  
Author(s):  
Yun-Shen Chan ◽  
Jonathan Göke ◽  
Xinyi Lu ◽  
Nandini Venkatesan ◽  
Bo Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Pluripotent Stem Cell ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Cell Reprogramming ◽  
Induced Pluripotent

scholarly journals Relaxed 3D genome conformation facilitates the pluripotent to totipotent state transition in embryonic stem cells

2020 ◽  
Author(s):  
Jiali Yu ◽  
Yezhang Zhu ◽  
Jiahui Gu ◽  
Chaoran Xue ◽  
Long Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Genome Organization ◽  
Critical Role ◽  
Embryonic Stem ◽  
List Type ◽  
Down Regulation ◽  
Chromatin Loops ◽  
3D Genome

SUMMARYThe 3D genome organization is crucial for gene regulation. Although recent studies have revealed a uniquely relaxed genome conformation in totipotent early blastmeres of both fertilized and cloned embryos, how weakened higher-order chromatin structure is functionally linked to totipotency acquisition remains elusive. Using low-input Hi-C, ATAC-seq, and ChIP-seq, we systematically examined the dynamics of 3D genome and epigenome during pluripotency-to-totipotency transition in mouse embryonic stem cells (ESCs). The totipotent 2-cell-embro-like cells (2CLCs) exhibit more relaxed chromatin architecture compared to ESCs, including global weakening of both enhancer-promoter interactions and TAD insulation. While the former leads to inactivation of ESC enhancers and down-regulation of pluripotent genes, the latter may facilitate contacts between the new enhancers arising in 2CLCs and neighboring 2C genes. Importantly, disruption of chromatin loops by depleting CTCF or cohesin promotes ESC to 2CLC transition. Our results thus establish a critical role of 3D genome organization in totipotency acquisition.HIGHLIGHTSGlobal weakening of the 3D genome conformation during ESC to 2CLC transitionLoss of enhancer-promoter loops and down-regulation of pluripotent genes in 2CLCsInactivation of ESC enhancers and formation of new enhancers in 2CLCsDisruption of chromatin loops by depleting CTCF or cohesin promotes 2CLC emergence

Critical role of type 2 ryanodine receptor in mediating activity-dependent neurogenesis from embryonic stem cells

Cell Calcium ◽  
2008 ◽  
Vol 43 (5) ◽  
pp. 417-431 ◽  
Author(s):  
Hui-Mei Yu ◽  
Jing Wen ◽  
Rong Wang ◽  
Wan-Hua Shen ◽  
Shumin Duan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Ryanodine Receptor ◽  
Critical Role ◽  
Embryonic Stem ◽  
Activity Dependent

scholarly journals The Role of E3s in Regulating Pluripotency of Embryonic Stem Cells and Induced Pluripotent Stem Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1168
Author(s):  
Yahong Wu ◽  
Weiwei Zhang
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
E3 Ligases ◽  
Somatic Cell Reprogramming ◽  
Age Related ◽  
Induced Pluripotent

Pluripotent embryonic stem cells (ESCs) are derived from early embryos and can differentiate into any type of cells in living organisms. Induced pluripotent stem cells (iPSCs) resemble ESCs, both of which serve as excellent sources to study early embryonic development and realize cell replacement therapies for age-related degenerative diseases and other cell dysfunction-related illnesses. To achieve these valuable applications, comprehensively understanding of the mechanisms underlying pluripotency maintenance and acquisition is critical. Ubiquitination modifies proteins with Ubiquitin (Ub) at the post-translational level to monitor protein stability and activity. It is extensively involved in pluripotency-specific regulatory networks in ESCs and iPSCs. Ubiquitination is achieved by sequential actions of the Ub-activating enzyme E1, Ub-conjugating enzyme E2, and Ub ligase E3. Compared with E1s and E2s, E3s are most abundant, responsible for substrate selectivity and functional diversity. In this review, we focus on E3 ligases to discuss recent progresses in understanding how they regulate pluripotency and somatic cell reprogramming through ubiquitinating core ESC regulators.

scholarly journals TRIM66 reads unmodified H3R2K4 and H3K56ac to respond to DNA damage in embryonic stem cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiajing Chen ◽  
Zikang Wang ◽  
Xudong Guo ◽  
Fudong Li ◽  
Qingtao Wei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Embryonic Stem Cells ◽  
Critical Role ◽  
Embryonic Stem ◽  
Genomic Stability ◽  
Vital Role ◽  
Damage Repair ◽  
The Relationship

Abstract Recognition of specific chromatin modifications by distinct structural domains within “reader” proteins plays a critical role in the maintenance of genomic stability. However, the specific mechanisms involved in this process remain unclear. Here we report that the PHD-Bromo tandem domain of tripartite motif-containing 66 (TRIM66) recognizes the unmodified H3R2-H3K4 and acetylated H3K56. The aberrant deletion of Trim66 results in severe DNA damage and genomic instability in embryonic stem cells (ESCs). Moreover, we find that the recognition of histone modification by TRIM66 is critical for DNA damage repair (DDR) in ESCs. TRIM66 recruits Sirt6 to deacetylate H3K56ac, negatively regulating the level of H3K56ac and facilitating the initiation of DDR. Importantly, Trim66-deficient blastocysts also exhibit higher levels of H3K56ac and DNA damage. Collectively, the present findings indicate the vital role of TRIM66 in DDR in ESCs, establishing the relationship between histone readers and maintenance of genomic stability.

scholarly journals Evidence for a Critical Role of Catecholamines for Cardiomyocyte Lineage Commitment in Murine Embryonic Stem Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70913 ◽  
Author(s):  
Martin Lehmann ◽  
Filomain Nguemo ◽  
Vilas Wagh ◽  
Kurt Pfannkuche ◽  
Jürgen Hescheler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Critical Role ◽  
Embryonic Stem ◽  
Lineage Commitment ◽  
Murine Embryonic Stem Cells
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