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ZFP982, a novel regulator for self‐renewal of mouse stem cells potentially through interaction with YAP1, the major co-activator of the Hippo pathway

ABSTRACT: Network-based expression analyses serve identifying novel biological interactions based on comparing transcriptional differences of mouse embryonic stem cells (mESC) and differentiated cells (DC). By comparing the transcriptional profiles of mESC and DCs, we identified zinc finger protein 982 (Zfp982), a new gene specifically expressed by mESC. Co-expression analyses indicated transcriptional overlap of Zfp982 with yes-associated protein 1 (Yap1) and further stem cell markers. Gain- and loss-of-function experiments in P19 and mESC established a role of Zfp982 in conferring cell pluripotency and/or differentiation. Our results showed that Zfp982 expression decreased with progressive differentiation of stem cells and knock down of Zfp982 allowed for neural differentiation in stem cells. On the contrary, OEession of Zfp982 prevented differentiation and maintained stem cell characteristics in mESC. Further functional analyses suggested a potential role of the ZFP982 protein in the Hippo signaling pathway. Quantitative proteomics and co-immunoprecipitation (co-IP) revealed interaction of ZFP982 with YAP1, the major co-activator of the Hippo pathway. ZFP982 bound and induced genes important for conferring stemness of mESC, including Nanog, Zfp42 and Dppa3. Collectively, our findings established the function of ZFP982 in maintaining stem cell pluripotency possibly through interaction with the Hippo pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE141505 | GEO | 2024/12/31

REPOSITORIES: GEO

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Project description:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation. This model is described in the article: In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach. Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R BMC Genomics, 2009, 10:314 Abstract: BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency. RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation. CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies. This model is hosted on BioModels Database and identified by: MODEL1305010000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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ZFP982, a novel regulator for self‐renewal of mouse stem cells potentially through interaction with YAP1, the major co-activator of the Hippo pathway

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