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One common symptom observed in patients with anthrax is thrombocytopenia, which has also been observed in mice injected with LT. Our previous study demonstrated that LT induces thrombocytopenia by suppressing megakaryopoiesis, but the precise molecular mechanisms behind this phenomenon remain unknown. In this study, we utilized 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced megakaryocytic differentiation in human erythroleukemia (HEL) cells to identify genes involved in LT-induced megakaryocytic suppression. Through cDNA microarray analysis, we identified Dachshund homolog 1 (DACH1) as a gene that was upregulated upon TPA treatment but downregulated in the presence of TPA and LT, purified from the culture supernatants of B. anthracis. To investigate the function of DACH1 in megakaryocytic differentiation, we employed short hairpin RNA technology to knock down DACH1 expression in HEL cells and assessed its effect on differentiation. Our data revealed that the knockdown of DACH1 expression suppressed megakaryocytic differentiation, particularly in polyploidization. We demonstrated that one mechanism by which B. anthracis LT induces suppression of polyploidization in HEL cells is through the cleavage of MEK1\/2. This cleavage results in the downregulation of the ERK signaling pathway, thereby suppressing DACH1 gene expression and inhibiting polyploidization. Additionally, we found that known megakaryopoiesis-related genes, such as FOSB, ZFP36L1, RUNX1, FLI1, AHR, and GFI1B genes may be positively regulated by DACH1. Furthermore, we observed an upregulation of DACH1 during in vitro differentiation of CD34\u2013megakaryocytes and downregulation of DACH1 in patients with thrombocytopenia. In summary, our findings shed light on one of the molecular mechanisms behind LT-induced thrombocytopenia and unveil a previously unknown role for DACH1 in megakaryopoiesis.<\/jats:p>","DOI":"10.3390\/ijms25063102","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T08:59:37Z","timestamp":1709801977000},"page":"3102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dachshund Homolog 1: Unveiling Its Potential Role in Megakaryopoiesis and Bacillus anthracis Lethal Toxin-Induced Thrombocytopenia"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-6274","authenticated-orcid":false,"given":"Guan-Ling","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"},{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-3485","authenticated-orcid":false,"given":"Hsin-Hou","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Shan","family":"Liou","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ling","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Hua","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Kong","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Yuan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Mennonite Christian Hospital, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Chih","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Mennonite Christian Hospital, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2251-6900","authenticated-orcid":false,"given":"Tso-Fu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"},{"name":"Department of Medicine, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Buddhist Tzu Chi Stem Cells Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Chao","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"},{"name":"Department of Medicine, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Buddhist Tzu Chi Stem Cells Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyh-Hwa","family":"Kau","sequence":"additional","affiliation":[{"name":"Institute of Preventive Medicine, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Hsien","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Preventive Medicine, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3895-8057","authenticated-orcid":false,"given":"Hui-Ling","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Preventive Medicine, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1994-7355","authenticated-orcid":false,"given":"Der-Shan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1146\/annurev.micro.55.1.647","article-title":"Anthrax","volume":"55","author":"Mock","year":"2001","journal-title":"Annu. 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