دورية أكاديمية
Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates by cleaving TFIIA.
| العنوان: | Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates by cleaving TFIIA. |
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| المؤلفون: | Niizuma H; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan., Searleman AC; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Takeda S; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Armstrong SA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Park CY; Department of Pathology, NYU School of Medicine, New York, New York, USA., Cheng EH; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Hsieh JJ; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. |
| المصدر: | JCI insight [JCI Insight] 2021 Aug 09; Vol. 6 (15). Date of Electronic Publication: 2021 Aug 09. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Endopeptidases*/genetics , Endopeptidases*/metabolism, Abnormalities, Multiple/*genetics , Fetal Development/*physiology , Transcription Factor TFIIA/*genetics, Animals ; Embryo, Mammalian ; Hematopoietic Stem Cells ; Histone Code/genetics ; Histone-Lysine N-Methyltransferase/metabolism ; Mice ; Mice, Knockout ; Mutation ; Myeloid-Lymphoid Leukemia Protein/metabolism ; RNA Cleavage ; Stem Cell Transplantation |
| مستخلص: | Taspase1, a highly conserved threonine protease encoded by TASP1, cleaves nuclear histone-modifying factors and basal transcription regulators to orchestrate diverse transcription programs. Hereditary loss-of-function mutation of TASP1 has recently been reported in humans as resulting in an anomaly complex syndrome, which manifests with hematological, facial, and skeletal abnormalities. Here, we demonstrate that Taspase1-mediated cleavage of TFIIAα-β, rather than of MLL1 or MLL2, in mouse embryos was required for proper fetal liver hematopoiesis and correct segmental identities of the axial skeleton. Homozygous genetic deletion of Taspase1 disrupted embryonic hematopoietic stem cell self-renewal and quiescence states and axial skeleton fates. Strikingly, mice carrying knockin noncleavable mutations of TFIIAα-β, a well-characterized basal transcription factor, displayed more pronounced fetal liver and axial skeleton defects than those with noncleavable MLL1 and MLL2, 2 trithorax group histone H3 trimethyl transferases. Our study offers molecular insights into a syndrome in humans that results from loss of TASP1 and describes an unexpected role of TFIIAα-β cleavage in embryonic cell fate decisions. |
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| معلومات مُعتمدة: | P30 CA008748 United States CA NCI NIH HHS; R01 CA119008 United States CA NCI NIH HHS; R01 CA138505 United States CA NCI NIH HHS; U01 CA138505 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Development; Embryonic development; Genetic diseases; Stem cell transplantation; Stem cells |
| المشرفين على المادة: | 0 (Transcription Factor TFIIA) 149025-06-9 (Myeloid-Lymphoid Leukemia Protein) EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) EC 2.1.1.43 (Kmt2a protein, mouse) EC 2.1.1.43 (Kmt2b protein, mouse) EC 3.4.- (Endopeptidases) EC 3.4.22.- (taspase1, mouse) |
| تواريخ الأحداث: | Date Created: 20210622 Date Completed: 20220225 Latest Revision: 20220401 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8410044 |
| DOI: | 10.1172/jci.insight.149382 |
| PMID: | 34156981 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.149382 |