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| 2. |
- Risal, Sanjiv, et al.
(författare)
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MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice
- 2017
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Ingår i: Cell Discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs. We generated a mouse model where we specifically deleted Mastl in PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion of Mastl in PGCs did not prevent mitotic entry, but led to a failure of the cells to proceed beyond metaphase-like stage, indicating that MASTL-mediated molecular events are indispensable for anaphase entry in PGCs. These mitotic defects further led to the death of Mastl-null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in the Mastl-null PGCs was rescued by simultaneous deletion of Ppp2r1a (a subunit of PP2A). Thus, our results demonstrate that MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis.
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| 3. |
- Tu, Zhaowei, et al.
(författare)
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Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase I independent of Cdk2 activation
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:3, s. 592-597
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Tidskriftsartikel (refereegranskat)abstract
- Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosomemovement duringmeiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I male and female germ cells in mice, and plays an essential role in the telomere-NE attachment. Deletion of Spdya in mice disrupts telomere-NE attachment, and this impairs homologous pairing and synapsis and leads to zygotene arrest in male and female germ cells. In addition, we have identified a telomere localization domain on Speedy A covering the distal N terminus and the Cdk2-binding Ringo domain, and this domain is essential for the localization of Speedy A to telomeres. Furthermore, we found that the binding of Cdk2 to Speedy A is indispensable for Cdk2' s localization on telomeres, suggesting that Speedy A and Cdk2 might be the initial components that are recruited to the NE for forming the meiotic telomere complex. However, Speedy A-Cdk2-mediated telomere-NE attachment is independent of Cdk2 activation. Our results thus indicate that Speedy A and Cdk2 might mediate the initial telomere-NE attachment for the efficient assembly of the telomere complex that is essential for meiotic prophase I progression.
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| 4. |
- Wang, L. N., et al.
(författare)
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Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis
- 2018
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Ingår i: Cell Death and Differentiation. - 1350-9047. ; 25:6, s. 1174-1188
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Tidskriftsartikel (refereegranskat)abstract
- Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Ttf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1/-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to end fusion due to the failure of recruiting meiosis specific telomere associated proteins. Further investigations uncovered that TRF1 could directly interact with Speedy A, and Speedy A might work as a scaffold protein to further recruit Cdk2, thus protecting telomeres from fusion at this stage. Together, our results reveal a novel mechanism of TRF1, Speedy A, and Cdk2 in protecting telomere from fusion in a highly crowded microenvironment during meiosis.
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| 5. |
- Yang, Qinsong, et al.
(författare)
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Genomic basis of the distinct biosynthesis of β-glucogallin, a biochemical marker for hydrolyzable tannin production, in three oak species
- 2024
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Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137.
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Tidskriftsartikel (refereegranskat)abstract
- Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in grape wine aging, feed additives, and human healthcare. However, the limited availability of a high-quality reference genome of oaks greatly hampered the recognition of the mechanism of HT biosynthesis. Here, high-quality reference genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and Quercus dentata) that have different HT contents were generated. Multi-omics studies were carried out to identify key genes regulating HT biosynthesis. In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast one-hybrid assays were used to reveal the transcriptional regulation. Our results revealed that β-glucogallin was a biochemical marker for HT production in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme for β-glucogallin biosynthesis. The differential expression of UGT84A13, rather than enzyme activity, was the main reason for different β-glucogallin and HT accumulation. Notably, sequence variations in UGT84A13 promoters led to different trans-activating activities of WRKY32/59, explaining the different expression patterns of UGT84A13 among the three species. Our findings provide three high-quality new reference genomes for oak trees and give new insights into different transcriptional regulation for understanding β-glucogallin and HT biosynthesis in closely related oak species.
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| 6. |
- Lin, Zhaowei, et al.
(författare)
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Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells.
- 2014
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Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-1015 .- 1792-0981. ; 7:3, s. 625-629
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow-derived mesenchymal stem cells (MSCs) are dominant seed cell sources for bone regeneration. Bone morphogenetic proteins (BMPs) initiate cartilage and bone formation in a sequential cascade. Vascular endothelial growth factor (VEGF) is an essential coordinator of extracellular matrix remodeling, angiogenesis and bone formation. In the present study, the effects of the vascular endothelial growth factor 165 (VEGF165) and bone morphogenetic protein 2 (BMP2) genes on bone regeneration were investigated by the lentivirus-mediated cotransfection of the two genes into rat bone marrow-derived MSCs. The successful co-expression of the two genes in the MSCs was confirmed using quantitative polymerase chain reaction (qPCR) and western blot analysis. The results of alizarin red and alkaline phosphatase (ALP) staining at 14 days subsequent to transfection showed that the area of staining in cells transfected with BMP2 alone was higher than that in cells transfected with BMP2 and VEGF165 or untransfected control cells, while the BMP2 + VEGF165 group showed significantly more staining than the untransfected control. This indicated that BMP2 alone exhibited a stronger effect in bone regeneration than BMP2 in combination with VEGF165. Similarly, in inducing culture medium, the ALP activity of the BMP2 + VEGF165 group was notably suppressed compared with that of the BMP2 group. The overexpression of VEGF165 inhibited BMP2-induced MSC differentiation and osteogenesis in vitro. Whether or not local VEGF gene therapy is likely to affect bone regeneration in vivo requires further investigation.
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| 7. |
- Xu, Zhaowei, et al.
(författare)
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Acetylation of Checkpoint suppressor 1 enhances its stability and promotes the progression of triple-negative breast cancer
- 2022
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Ingår i: Cell Death Discovery. - : Springer Nature. - 2058-7716. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Checkpoint suppressor 1 (CHES1), a transcriptional regulator, had been dysregulated in many types of malignancies including breast cancer, and its expression level is strongly associated with progression and prognosis of patients. However, the underlying regulatory mechanisms of CHES1 expression in the breast cancer and the effects of post-translational modifications (PTMs) on its functional performance remain to be fully investigated. Herein, we found that CHES1 had a high abundance in triple-negative breast cancer (TNBC) and its expression was tightly associated with malignant phenotype and poor outcomes of patients. Furthermore, we confirmed that CHES1 was an acetylated protein and its dynamic modification was mediated by p300 and HDAC1, and CHES1 acetylation enhanced its stability via decreasing its ubiquitination and degradation, which resulted in the high abundance of CHES1 in TNBC. RNA-seq and functional study revealed that CHES1 facilitated the activation of oncogenic genes and pathways leading to proliferation and metastasis of TNBC. Taken together, this research established a novel regulatory role of acetylation on the stability and activity of CHES1. The results demonstrate the significance of CHES1 acetylation and underlying mechanisms in the progression of TNBC, offering new potential candidate for molecular-targeted therapy in breast cancer.
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