scholarly journals Essential requirement of mammalian Pumilio family in embryonic development

2018 ◽  
Vol 29 (24) ◽  
pp. 2922-2932 ◽  
Author(s):  
Kaibo Lin ◽  
Shikun Zhang ◽  
Qinghua Shi ◽  
Mengyi Zhu ◽  
Liuze Gao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Development ◽  
Rna Binding ◽  
Germ Line ◽  
Embryonic Stem ◽  
Cell Development ◽  
Luciferase Reporter ◽  
Essential Requirement ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

Mouse PUMILIO1 (PUM1) and PUMILIO2 (PUM2) belong to the PUF (Pumilio/FBF) family, a highly conserved RNA binding protein family whose homologues play critical roles in embryonic development and germ line stem cell maintenance in invertebrates. However, their roles in mammalian embryonic development and stem cell maintenance remained largely uncharacterized. Here we report an essential requirement of the Pum gene family in early embryonic development. A loss of both Pum1 and Pum2 genes led to gastrulation failure, resulting in embryo lethality at E8.5. Pum-deficient blastocysts, however, appeared morphologically normal, from which embryonic stem cells (ESCs) could be established. Both mutant ESCs and embryos exhibited reduced growth and increased expression of endoderm markers Gata6 and Lama1, making defects in growth and differentiation the likely causes of gastrulation failure. Furthermore, ESC Gata6 transcripts could be pulled down via PUM1 immunoprecipitation and mutation of conserved PUM-binding element on 3′UTR (untranslated region) of Gata6 enhanced the expression of luciferase reporter, implicating PUM-mediated posttranscriptional regulation of Gata6 expression in stem cell development and cell lineage determination. Hence, like its invertebrate homologues, mouse PUM proteins are conserved posttranscriptional regulators essential for embryonic and stem cell development.

scholarly journals Methionine metabolism is essential for SIRT 1‐regulated mouse embryonic stem cell maintenance and embryonic development

2017 ◽  
Vol 36 (21) ◽  
pp. 3175-3193 ◽  
Author(s):  
Shuang Tang ◽  
Yi Fang ◽  
Gang Huang ◽  
Xiaojiang Xu ◽  
Elizabeth Padilla‐Banks ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Development ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Methionine Metabolism ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

scholarly journals Normal microRNA Maturation and Germ-Line Stem Cell Maintenance Requires Loquacious, a Double-Stranded RNA-Binding Domain Protein

PLoS Biology ◽  
2005 ◽  
Vol 3 (7) ◽  
pp. e236 ◽  
Author(s):  
Klaus Förstemann ◽  
Yukihide Tomari ◽  
Tingting Du ◽  
Vasily V Vagin ◽  
Ahmet M Denli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Rna Binding ◽  
Germ Line ◽  
Binding Domain ◽  
Double Stranded Rna ◽  
Stem Cell Maintenance ◽  
Germ Line Stem Cell ◽  
Domain Protein ◽  
Rna Binding Domain ◽  
Cell Maintenance

scholarly journals The Role of Ubiquitination in Regulating Embryonic Stem Cell Maintenance and Cancer Development

2019 ◽  
Vol 20 (11) ◽  
pp. 2667 ◽  
Author(s):  
Dian Wang ◽  
Fan Bu ◽  
Weiwei Zhang
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cancer Biology ◽  
Embryonic Stem ◽  
Developmental Defects ◽  
Stem Cell Maintenance ◽  
Substrate Protein ◽  
Cellular Events ◽  
Ubiquitin Conjugating Enzymes ◽  
Cell Maintenance

Ubiquitination regulates nearly every aspect of cellular events in eukaryotes. It modifies intracellular proteins with 76-amino acid polypeptide ubiquitin (Ub) and destines them for proteolysis or activity alteration. Ubiquitination is generally achieved by a tri-enzyme machinery involving ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2) and ubiquitin ligases (E3). E1 activates Ub and transfers it to the active cysteine site of E2 via a transesterification reaction. E3 coordinates with E2 to mediate isopeptide bond formation between Ub and substrate protein. The E1-E2-E3 cascade can create diverse types of Ub modifications, hence effecting distinct outcomes on the substrate proteins. Dysregulation of ubiquitination results in severe consequences and human diseases. There include cancers, developmental defects and immune disorders. In this review, we provide an overview of the ubiquitination machinery and discuss the recent progresses in the ubiquitination-mediated regulation of embryonic stem cell maintenance and cancer biology.

scholarly journals The RNA‐binding protein Imp2 regulates oxidative phosporylation that is key to glioblastoma cancer stem cell maintenance

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Michalina Janiszewska ◽  
Mario-Luca Suva ◽  
Riekelt H. Houtkooper ◽  
Virginie Clement-Schatlo ◽  
Ivan Stamenkovic
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

scholarly journals Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs

2020 ◽  
Vol 117 (7) ◽  
pp. 3603-3609 ◽  
Author(s):  
Fan Zou ◽  
Renjun Tu ◽  
Bo Duan ◽  
Zhenlin Yang ◽  
Zhaohua Ping ◽  
...  
Keyword(s):  
Stem Cell ◽  
Rna Binding ◽  
Germ Line ◽  
Adult Stem Cell ◽  
Cell Development ◽  
Rna Modification ◽  
Proliferation And Differentiation ◽  
Germ Line Stem Cell ◽  
Rna Complex

5-Methylcytosine (m5C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m5C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in the Drosophila ovary by preferentially binding to m5C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in the Drosophila ovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m5C RNA in vitro. Moreover, YPS also preferentially binds to m5C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m5C binding. Overexpression of RNA-binding–defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m5C RNA modification plays an important role in adult stem cell development.

scholarly journals Loss of Mob1a/b impairs the differentiation of mouse embryonic stem cells into the three germ layer lineages

2019 ◽  
Vol 51 (11) ◽  
pp. 1-12 ◽  
Author(s):  
June Sung Bae ◽  
Sun Mi Kim ◽  
Yoon Jeon ◽  
Juyeon Sim ◽  
Ji Yun Jang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hippo Pathway ◽  
Critical Role ◽  
Embryonic Stem ◽  
Mouse Escs ◽  
Germ Layers ◽  
Stem Cell Maintenance ◽  
The Hippo Pathway ◽  
Cell Maintenance

AbstractThe Hippo pathway plays a crucial role in cell proliferation and apoptosis and can regulate stem cell maintenance and embryonic development. MOB kinase activators 1A and 1B (Mob1a/b) are key components of the Hippo pathway, whose homozygous deletion in mice causes early embryonic lethality at the preimplantation stage. To investigate the role of Mob1a/b in stem cell maintenance and differentiation, an embryonic stem cell (ESC) clone in which Mob1a/b could be conditionally depleted was generated and characterized. Although Mob1a/b depletion did not affect the stemness or proliferation of mouse ESCs, this depletion caused defects in differentiation into the three germ layers. Yap knockdown rescued the in vitro and in vivo defects in differentiation caused by Mob1a/b depletion, suggesting that differentiation defects caused by Mob1a/b depletion were Yap-dependent. In teratoma experiments, Yap knockdown in Mob1a/b-depleted ESCs partially restored defects in differentiation, indicating that hyperactivation of Taz, another effector of the Hippo pathway, inhibited differentiation into the three germ layers. Taken together, these results suggest that Mob1a/b or Hippo signaling plays a critical role in the differentiation of mouse ESCs into the three germ layers, which is dependent on Yap. These close relationship of the Hippo pathway with the differentiation of stem cells supports its potential as a therapeutic target in regenerative medicine.

scholarly journals The Importance of Ubiquitination and Deubiquitination in Cellular Reprogramming

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Bharathi Suresh ◽  
Junwon Lee ◽  
Kye-Seong Kim ◽  
Suresh Ramakrishna
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Embryonic Stem ◽  
Cellular Reprogramming ◽  
Stem Cell Maintenance ◽  
Opposite Action ◽  
Induced Pluripotent ◽  
Related Proteins ◽  
Cell Maintenance

Ubiquitination of core stem cell transcription factors can directly affect stem cell maintenance and differentiation. Ubiquitination and deubiquitination must occur in a timely and well-coordinated manner to regulate the protein turnover of several stemness related proteins, resulting in optimal embryonic stem cell maintenance and differentiation. There are two switches: an E3 ubiquitin ligase enzyme that tags ubiquitin molecules to the target proteins for proteolysis and a second enzyme, the deubiquitinating enzyme (DUBs), that performs the opposite action, thereby preventing proteolysis. In order to maintain stemness and to allow for efficient differentiation, both ubiquitination and deubiquitination molecular switches must operate properly in a balanced manner. In this review, we have summarized the importance of the ubiquitination of core stem cell transcription factors, such as Oct3/4, c-Myc, Sox2, Klf4, Nanog, and LIN28, during cellular reprogramming. Furthermore, we emphasize the role of DUBs in regulating core stem cell transcriptional factors and their function in stem cell maintenance and differentiation. We also discuss the possibility of using DUBs, along with core transcription factors, to efficiently generate induced pluripotent stem cells. Our review provides a relatively new understanding regarding the importance of ubiquitination/deubiquitination of stem cell transcription factors for efficient cellular reprogramming.

scholarly journals Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance

2015 ◽  
Vol 1 (10) ◽  
pp. e1500723 ◽  
Author(s):  
Oleg Fedorov ◽  
Josefina Castex ◽  
Cynthia Tallant ◽  
Dafydd R. Owen ◽  
Sarah Martin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Protein Interaction ◽  
Embryonic Stem ◽  
High Specificity ◽  
Stem Cell Differentiation ◽  
Head Group ◽  
Stem Cell Maintenance ◽  
Trophoblast Stem ◽  
Cell Maintenance

Mammalian SWI/SNF [also called Brg/Brahma-associated factors (BAFs)] are evolutionarily conserved chromatin-remodeling complexes regulating gene transcription programs during development and stem cell differentiation. BAF complexes contain an ATP (adenosine 5′-triphosphate)–driven remodeling enzyme (either BRG1 or BRM) and multiple protein interaction domains including bromodomains, an evolutionary conserved acetyl lysine–dependent protein interaction motif that recruits transcriptional regulators to acetylated chromatin. We report a potent and cell active protein interaction inhibitor, PFI-3, that selectively binds to essential BAF bromodomains. The high specificity of PFI-3 was achieved on the basis of a novel binding mode of a salicylic acid head group that led to the replacement of water molecules typically maintained in other bromodomain inhibitor complexes. We show that exposure of embryonic stem cells to PFI-3 led to deprivation of stemness and deregulated lineage specification. Furthermore, differentiation of trophoblast stem cells in the presence of PFI-3 was markedly enhanced. The data present a key function of BAF bromodomains in stem cell maintenance and differentiation, introducing a novel versatile chemical probe for studies on acetylation-dependent cellular processes controlled by BAF remodeling complexes.

scholarly journals The RNA binding protein Swm is critical for Drosophila melanogaster intestinal progenitor cell maintenance

2022 ◽  
Author(s):  
Ishara S Ariyapala ◽  
Kasun Buddika ◽  
Heather A Hundley ◽  
Brian Calvi ◽  
Nicholas Sokol
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Transcriptional Control ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Adult Stem Cell ◽  
Stem Cell Maintenance ◽  
And Function ◽  
Cell Maintenance

The regulation of stem cell survival, self-renewal, and differentiation is critical for the maintenance of tissue homeostasis. Although the involvement of signaling pathways and transcriptional control mechanisms in stem cell regulation have been extensively investigated, the role of post-transcriptional control is still poorly understood. Here we show that the nuclear activity of the RNA-binding protein Second Mitotic Wave Missing (Swm) is critical for Drosophila intestinal stem cells (ISCs) and their daughter cells, enteroblasts (EBs), to maintain their identity and function. Loss of swm in these intestinal progenitor cells leads ISCs and EBs to lose defined cell identities, fail to proliferate, and detach from the basement membrane, resulting in severe progenitor cell loss. swm loss further causes nuclear accumulation of poly(A)+ RNA in progenitor cells. Swm associates with transcripts involved in epithelial cell maintenance and adhesion, and the loss of swm, while not generally affecting the levels of these Swm-bound mRNAs, leads to elevated expression of proteins encoded by some of them, including the fly orthologs of Filamin and Talin. Taken together, this study indicates a role for Swm in adult stem cell maintenance, and raises the possibility that nuclear post-transcriptional gene regulation plays vital roles in controlling adult stem cell maintenance and function.

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