Synergistic Transcriptional and Post-Transcriptional Regulation of ESC Characteristics by Core Pluripotency Transcription Factors in Protein-Protein Interaction Networks

Li, Leijie; Zhang, Liangcai; Liu, Guiyou; Feng, Rennan; Jiang, Yongshuai; Yang, Lei; Zhang, Shihua; Liao, Mingzhi; Hua, Jinlian

doi:10.1371/journal.pone.0105180

Cited by 7 publications

(12 citation statements)

References 51 publications

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“…In our study, the highest concentration of IL-6 was observed in the supernatant from AT-MSCs and BM-MSCs, and the lowest was observed in SK-MSCs and SM-MSCs. These observations are in line with a study performed by Priciola et al[67] and by Li et al[69], which suggests that IL-6 is more efficiently produced by undifferentiated cells.…”

Section: Discussionsupporting

confidence: 93%

Similarities and differences between mesenchymal stem/progenitor cells derived from various human tissues

Kozlowska

Krawczenko

Futoma

et al. 2019

WJSC

149

113

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BACKGROUND Mesenchymal stromal/stem cells (MSCs) constitute a promising tool in regenerative medicine and can be isolated from different human tissues. However, their biological properties are still not fully characterized. Whereas MSCs from different tissue exhibit many common characteristics, their biological activity and some markers are different and depend on their tissue of origin. Understanding the factors that underlie MSC biology should constitute important points for consideration for researchers interested in clinical MSC application. AIM To characterize the biological activity of MSCs during longterm culture isolated from: bone marrow (BM-MSCs), adipose tissue (AT-MSCs), skeletal muscles (SM-MSCs), and skin (SK-MSCs). METHODS MSCs were isolated from the tissues, cultured for 10 passages, and assessed for: phenotype with immunofluorescence and flow cytometry, multipotency with differentiation capacity for osteo-, chondro-, and adipogenesis, stemness markers with qPCR for mRNA for Sox2 and Oct4, and genetic stability for p53 and c-Myc; 27 bioactive factors were screened using the multiplex ELISA array, and spontaneous fusion involving a co-culture of SM-MSCs with BM-MSCs or AT-MSCs stained with PKH26 (red) or PKH67 (green) was performed. RESULTS All MSCs showed the basic MSC phenotype; however, their expression decreased during the follow-up period, as confirmed by fluorescence intensity. The examined MSCs express CD146 marker associated with proangiogenic properties; however their expression decreased in AT-MSCs and SM-MSCs, but was maintained in BM-MSCs. In contrast, in SK-MSCs CD146 expression increased in late passages. All MSCs, except BM-MSCs, expressed PW1, a marker associated with differentiation capacity and apoptosis. BM-MSCs and AT-MSCs expressed stemness markers Sox2 and Oct4 in long-term culture. All MSCs showed a stable p53 and c-Myc expression. BM-MSCs and AT-MSCs maintained their differentiation capacity during the follow-up period. In contrast, SK-MSCs and SM-MSCs had a limited ability to differentiate into adipocytes. BM-MSCs and AT-MSCs revealed similarities in phenotype maintenance, capacity for multilineage differentiation, and secretion of bioactive factors. Because AT-MSCs fused with SM-MSCs as effectively as BM-MSCs, AT-MSCs may constitute an alternative source for BM-MSCs. CONCLUSION Long-term culture affects the biological activity of MSCs obtained from various tissues. The source of MSCs and number of passages are important considerations in regenerative medicine.

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Section: Discussionsupporting

confidence: 93%

Similarities and differences between mesenchymal stem/progenitor cells derived from various human tissues

Kozlowska

Krawczenko

Futoma

et al. 2019

WJSC

149

113

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“…Due to its key roles in ESCs, SALL4’s interactions with transcription factors crucial for pluripotency have also been explored. Two independent studies, using unbiased approaches of affinity purification of Oct4 followed by mass spectrometry, identified Sall4 to be one of its binding partners in mouse ESCs 131,132 . Both approaches identified components of the NuRD complex, raising the possibility that Sall4 may bridge the interaction between Oct4 and this epigenetic repressor complex.…”

Section: Molecular Dissection Of Sall4 Functions In Cellsmentioning

confidence: 99%

SALL4, the missing link between stem cells, development and cancer

Tatetsu

Kong

Gao

et al. 2016

Gene

109

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There is a growing body of evidence supporting that cancer cells share many similarities with embryonic stem cells (ESCs). For example, aggressive cancers and ESCs share a common gene expression signature that includes hundreds of genes. Since ESC genes are not present in most adult tissues, they could be ideal candidate targets for cancer-specific diagnosis and treatment. This is an exciting cancer-targeting model. The major hurdle to test this model is to identify the key factors/pathway(s) within ESCs that are responsible for the cancer phenotype. SALL4 is one of few genes that can establish this link. The first publication of SALL4 is on its mutation in a human inherited disorder with multiple developmental defects. Since then, over 300 papers have been published on various aspects of this gene in stem cells, development, and cancers. This review aims to summarize our current knowledge of SALL4, including a SALL4-based approach to classify and target cancers. Many questions about this important gene still remain unanswered, specifically, on how this gene regulates cell fates at a molecular level. Understanding SALL4’s molecular functions will allow development of specific targeted approaches in the future.

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“…Mounting evidence has shown that ESCs self-renewal is orchestrated by a variety of transcription factors, signaling molecules and RNA regulatory factors ( Huang et al, 2015 ; Abu-Dawud et al, 2018 ). Previous work has indicated that transcriptional and post-transcriptional modifications are important for the regulation of ESCs self-renewal ( Li et al, 2014 ). It has been reported that Oct4 and NANOG recruit LSD1 and bind to promoters of development-related genes, thereby controlling ESCs self-renewal by modulating H3K4 and H3K27 methylation ( Adamo et al, 2011 ; Whyte et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

LHPP-Mediated Histidine Dephosphorylation Suppresses the Self-Renewal of Mouse Embryonic Stem Cells

Xia

Yao

Cai

et al. 2021

Front. Cell Dev. Biol.

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Self-renewal of embryonic stem cells (ESCs) is orchestrated by a vast number of genes at the transcriptional and translational levels. However, the molecular mechanisms of post-translational regulatory factors in ESC self-renewal remain unclear. Histidine phosphorylation, also known as hidden phosphorylation, cannot be detected by conventional experimental methods. A recent study defined phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) as a histidine phosphatase, which regulates various biological behaviors in cells via histidine dephosphorylation. In this study, the doxycycline (DOX)-induced hLHPP-overexpressing mouse ESCs and mouse LHPP silenced mESCs were constructed. Quantitative polymerase chain reaction (qPCR), western blotting analysis, immunofluorescence, Flow cytometry, colony formation assays, alkaline phosphatase (AP) and bromodeoxyuridine (Brdu) staining were performed. We found that the histidine phosphorylation level was strikingly reduced following LHPP overexpression. Besides, the expression of Oct4 and Lefty1, indispensable genes in the process of ESCs self-renewal, was significantly down-regulated, while markers related to the differentiation were markedly elevated. Moreover, LHPP-mediated histidine dephosphorylation induced G0/G1 phase arrest in mESCs, suggesting LHPP was implicated in cell proliferation and cell cycle. Conversely, silencing of Lhpp promoted the self-renewal of mESCs and reversed the RA induced increased expression of genes associated with differentiation. Mechanistically, our findings suggested that the enzymatic active site of LHPP was the cysteine residue at position 226, not 53. LHPP-mediated histidine dephosphorylation lowered the expression levels of β-catenin and the cell cycle-related genes CDK4 and CyclinD1, while it up-regulated the cell cycle suppressor genes P21 and P27. Taken together, our findings reveal that LHPP-mediated histidine dephosphorylation plays a role in the self-renewal of ESCs. LHPP-mediated histidine dephosphorylation inhibited the self-renewal of ESCs by negatively regulating the Wnt/β-catenin pathway and downstream cell cycle-related genes, providing a new perspective and regulatory target for ESCs self-renewal.

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Synergistic Transcriptional and Post-Transcriptional Regulation of ESC Characteristics by Core Pluripotency Transcription Factors in Protein-Protein Interaction Networks

Cited by 7 publications

References 51 publications

Similarities and differences between mesenchymal stem/progenitor cells derived from various human tissues

Similarities and differences between mesenchymal stem/progenitor cells derived from various human tissues

SALL4, the missing link between stem cells, development and cancer

LHPP-Mediated Histidine Dephosphorylation Suppresses the Self-Renewal of Mouse Embryonic Stem Cells

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