ArticleThe Journal of experimental medicine2011
A genome-wide RNAi screen in mouse embryonic stem cells identifies Mp1 as a key mediator of differentiation.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Transcriptome Analysis of Key Genes Involved in the Initiation of Spermatogonial Stem Cell Differentiation.Genes · 2024Article
- Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2.The EMBO journal · 2020Article
- Identifying survival-associated modules from the dysregulated triplet network in glioblastoma multiforme.Journal of cancer research and clinical oncology · 2017Article
- Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells.Scientific data · 2017Article
- Deficiency of microRNAScience (New York, N.Y.) · 2017Article
- Src Family Kinases and p38 Mitogen-Activated Protein Kinases Regulate Pluripotent Cell Differentiation in Culture.PloS one · 2016Article
- Distribution Analyzer, a methodology for identifying and clustering outlier conditions from single-cell distributions, and its application to a Nanog reporter RNAi screen.BMC bioinformatics · 2015Article
- Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function.Scientific reports · 2015Article
- Ischemic preconditioning affects long-term cell fate through DNA damage-related molecular signaling and altered proliferation.The American journal of pathology · 2014Article
- Testicular cancer: biology and biomarkers.Virchows Archiv : an international journal of pathology · 2014Review
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- A genome-wide RNAi screen reveals MAP kinase phosphatases as key ERK pathway regulators during embryonic stem cell differentiation.PLoS genetics · 2012Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite intense investigation of intrinsic and extrinsic factors that regulate pluripotency, the process of initial fate commitment of embryonic stem (ES) cells is still poorly understood. We used a genome-wide short hairpin RNA screen in mouse ES cells to identify genes that are essential for initiation of differentiation. Knockdown of the scaffolding protein Mek binding protein 1 (Mp1, also known as Lamtor3 or Map2k1ip1) stimulated self-renewal of ES cells, blocked differentiation, and promoted proliferation. Fibroblast growth factor 4 (FGF4) signaling is required for initial fate commitment of ES cells. Knockdown of Mp1 inhibited FGF4-induced differentiation but did not alter FGF4-driven proliferation. This uncoupling of differentiation and proliferation was also observed when oncogenic Ras isoforms were overexpressed in ES cells. Knockdown of Mp1 redirected FGF4 signaling from differentiation toward pluripotency and up-regulated the pluripotency-related genes Esrrb, Rex1, Tcl1, and Sox2. We also found that human germ cell tumors (GCTs) express low amounts of Mp1 in the invasive embryonic carcinoma and seminoma histologies and higher amounts of Mp1 in the noninvasive carcinoma in situ precursor and differentiated components. Knockdown of Mp1 in invasive GCT cells resulted in resistance to differentiation, thereby showing a functional role for Mp1 both in normal differentiation of ES cells and in germ cell cancer.
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Registered trials
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