Ask about this productRelated genes to: PLAGL1 Blocking Peptide
- Gene:
- PLAGL1 NIH gene
- Name:
- PLAG1 like zinc finger 1
- Previous symbol:
- -
- Synonyms:
- ZAC, LOT1
- Chromosome:
- 6q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-02-17
- Date modifiied:
- 2019-04-23
Related products to: PLAGL1 Blocking Peptide
Related articles to: PLAGL1 Blocking Peptide
- Transcription factor (TF) networks are pivotal regulators of stem/progenitor cell fate. However, the regulatory mechanisms mediated by key TFs in adult periosteal stem/progenitor cells (PSPCs) remain poorly understood, impeding targeted therapies development for craniofacial bone regeneration. By integrating an analysis of regeneration-related, tissue-specific TF networks with insights from embryonic development, we demonstrate that the imprinted TF PLAGL1 is critical for the osteoblast differentiation of PSPCs and that the loss of Plagl1 compromises mandibular bone regeneration. Mechanistically, PLAGL1 transcriptionally activates TF Irx5 synergistically with TF KLF4, thereby inducing the expression of downstream osteogenic genes. Using the CRISPR-dCas9-Tet1-CD/sgRNA system, we develop a differentially methylated region-targeted therapeutic strategy to reactivate the maternal allele of Plagl1, leveraging its imprinted function to promote mandibular bone regeneration. This study delineates the PLAGL1-KLF4-IRX5 regulatory axis controlling osteoblast differentiation of PSPCs and further proposes an application strategy integrating TF modulation with epigenetic regulation for craniofacial bone regeneration. - Source: PubMed
Publication date: 2026/05/21
Yao EnhuiLiu YiliXu JingyiXu ZeqianHuang YileiZhou MingliangLin SihanJiang XinquanDu Jiahui - Periodontitis leads to alveolar bone resorption, driven by persistent periodontal pathogen infection. Such persistent infection creates a unique microenvironment conducive to sustained reactive oxygen species (ROS) production. Therefore, further investigation into approaches that simultaneously combat bacteria and improve the local microenvironment is needed. In the present study, a hydrogel drug delivery system was proposed, which employed an in-situ synthesis strategy of zeolitic imidazole frameworks 90 (ZIF90) encapsulating tungsten (W)-based polyoxometalate nanoparticles (ZIF90-W) to increase the W ratio and confer ATP responsiveness. ZIF90-W was incorporated into phenylboronic acid-modified quaternary ammonium salt chitosan hydrogel (QPT hydrogel), forming QPT@ZIF90-W hydrogel with responsive release properties in the periodontal pocket. Results demonstrated that QPT@ZIF90-W hydrogel exhibited over 90% antibacterial efficacy against periodontal pathogens. Besides, QPT@ZIF90-W significantly promoted osteogenic differentiation of MC3T3-E1 cells after scavenging mitochondrial ROS and total ROS. Mechanistically, the pro-osteogenic effect of QPT@ZIF90-W hydrogel was associated with the significant upregulation of Plagl1, following oxidative stress elimination and subsequent activating the Wnt signaling pathway, according to the transcriptome sequencing results. Concurrently, in vivo experiments demonstrated that QPT@ZIF90-W hydrogel treatment, compared with other groups, reduced inflammatory cell infiltration, upregulated Plagl1 and osteogenesis related proteins, and partially ameliorated alveolar bone resorption. In summary, QPT@ZIF90-W is characterized by synergistic antibacterial effect and ROS scavenging capability. These dual activities reshape the oxidative microenvironment and then activate Plagl1/Wnt pathway to promote osteogenesis, which offer a novel and potential strategy for the precise treatment of periodontitis-induced bone defects. - Source: PubMed
Publication date: 2026/05/14
Yu ZhenyuanLi YuchaoZhang ShuweiCao RuoyanLiu KunDeng JiaqiYang ZeWang HongyanWang QiangMiao LeiHu BoPan Yaping - MicroRNAs direct downregulation of target mRNAs. Sometimes, however, this regulatory paradigm inverts, and a target RNA triggers degradation of a microRNA. This target-directed microRNA degradation (TDMD) requires ZSWIM8. mice exhibit reduced growth and perinatal lethality, accompanied by stabilization of >40 microRNAs. Nonetheless, studies of TDMD function in mammals have been limited because only two TDMD-triggering RNAs have been identified in mice. Here, we computationally identify and validate five new TDMD-triggering sites in mouse models. One site in and two sites in direct degradation of miR-335-3p, showing that in mammals, two sites in the same transcript and multiple sites in different transcripts can collaborate to destabilize a microRNA. Moreover, sites in and direct degradation of miR-322 and miR-503, respectively. Mice lacking the and sites were smaller, demonstrating that target-directed degradation of miR-322 and miR-503 promotes growth. Both miR-335-3p and are maternally imprinted, implying their participation in parental conflict, but their corresponding triggers or target microRNA partners are not imprinted. Thus, 3' UTRs can participate in parental conflict not only by regulating protein production but also by engaging TDMD to access an additional layer of regulation within a network of imprinted and biallelic genes. - Source: PubMed
Publication date: 2026/04/01
Lin Daniel HElcavage Lara EKhalizeva EkaterinaBartel David P - Müller glia arise from late-stage retinal progenitor cells (RPCs) as a distinct lineage that diverges from neurogenic trajectories. Here, we identify the maternally imprinted gene Plagl1 as a key transcriptional regulator of gliogenesis in the murine retina. Plagl1 is expressed during the RPC-to-glia transition and is dynamically regulated in Müller glia following injury. To define its developmental role, we analyzed Plagl1⁺/⁻pat null mutant retinas at postnatal day 7 (P7), when central retinal gliogenesis is complete. In the absence of Plagl1, Sox9 ⁺ glial/precursor cells were displaced and proliferated ectopically, with structural dysmorphologies, reactive gliosis, and impaired visual processing persisting into later postnatal stages. Bulk RNA-seq and ATAC-seq revealed widespread reductions in chromatin accessibility and transcriptional dysregulation affecting epigenetic modifiers, translational machinery, fate-specifying transcription factors, cell cycle regulators, and signaling pathways. Single-cell pseudobulk analysis showed that Plagl1 loss disrupts chromatin, transcriptional, and translational programs specifically within Sox9 ⁺ cells, encompassing Müller glia and precursor populations, pinpointing these cells as the source of defects in Plagl1⁺/⁻pat retinas. Notch signaling was elevated in Plagl1-deficient glia, and genetic activation at P14 displaced Sox9 ⁺ glial cells, without inducing proliferation. Similarly, conditional deletion of Plagl1 in postnatal Müller glia at P14 disrupted positioning and not cell cycle exit, confirming a cell-autonomous requirement for Müller glia positioning that is independent of proliferation control. Since these conditional manipulations could only be performed at P14 at the earliest, they reveal Plagl1's later functions in postmitotic glia and complement, rather than mirror, the earlier P7 mixed RPC/glial null phenotype. Together these findings establish Plagl1 as a critical regulator of the late-stage RPC to Müller glia transition, acting through coordinated control of chromatin accessibility and gene expression programs to ensure timely cell cycle exit. This function aligns with Plagl1's broader tumor suppressor role in stabilizing postmitotic, differentiated cell states across tissues. - Source: PubMed
Publication date: 2026/03/18
Touahri YacinePak AlissaDavid Luke AjayHanna JosephLiu HedyXiao YuchengBelfiore LaurenIlnytskyy Yaroslavvan Oosten EdwinTachibana NobuhikoAdnani LataZhao JiayiHoffman MaryDixit RajivZinyk DawnGuidos Cynthia JEnzmann VolkerBi PengpengAubert IsabelleJournot LaurentKovalchuk IgorSauvé YvesBiernaskie JeffWang ChaoOkawa SatoshiDel Sol AntonioSchuurmans Carol - The 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) classification formalized routine molecular profiling, and DNA-methylation studies have since delineated PLAG-family-altered CNS entities: PLAGL1 fusion-positive supratentorial neuroepithelial tumors (NET_PLAGL1) and embryonal tumors with PLAGL1/PLAGL2 amplification. PLAG1 fusions with diverse partners have been reported in CNS embryonal tumors, but have not been described in supratentorial neuroepithelial tumors to date. We describe two pediatric supratentorial ependymal tumors with novel PLAG1 fusions that do not match any 2021 WHO-defined entity or any PLAG-family-related entity recently reported in the literature. Case 1 (4-year-old boy) had a 7.6-cm left lateral ventricular mass with edema and heterogeneous enhancement; gross total resection was performed without adjuvant therapy (alive at 8 months). Histology showed diffusely low cellularity with small- to medium-sized round nuclei, minimal atypia, and focal calcifications; no ependymal rosettes, branching vessels, or clear-cell change. Tumor cells were positive for GFAP and H3K27me3, and negative for Desmin, EMA, OLIG2, L1CAM, NF-κB and H3K27M. The MIB-1 labeling index was ~ 5%. RNA-seq identified TNC::PLAG1 fusion; FISH showed PLAG1 rearrangement. DNA methylation clustered with spinal subependymoma, despite supratentorial location. Case 2 (4-year-old girl) had a 1.4 × 1.1 cm left parahippocampal lesion; resected without adjuvant therapy (alive at 4 months). Histology showed low-to-moderate cellularity with diffuse microcystic change, focal clear/vacuolated cells, and delicate branching vessels. Tumor cells were positive for GFAP, EMA, L1CAM, H3K27me3 and ATRX, and negative for EMA, Desmin, NF-κB, OLIG2, H3K27M, and CD34 (MIB-1 ~ 2%). RNA-seq identified TXNIP::PLAG1 fusion. Methylation did not reach a class threshold. Both cases ultimately warrant a final diagnosis of ependymal tumor, not elsewhere classified. To our knowledge, TNC::PLAG1 and TXNIP::PLAG1 are first-ever fusions reported in any tumor type. They also represent the first PLAG1 fusions identified in pediatric supratentorial ependymal tumors. These cases highlight the value of integrating histology, methylation profiling, and fusion detection, and suggest a new candidate supratentorial ependymal subtype with PLAG1 fusions, pending validation in larger series. - Source: PubMed
Publication date: 2026/02/04
Zheng LinmaoZhang JinyanHou JingLuo TaoPan XiuyiLong ZhongmingSu ZhengzhengZhou QiaoWei YuyanChen Ni