GATA1 controls numbers of hematopoietic progenitors and their response to autoimmune neuroinflammation.
GATA1 controls numbers of hematopoietic progenitors and their response to autoimmune neuroinflammation.
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DOI：
10.1182/bloodadvances.2022008234
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发表时间：
2022-12-13
期刊：
影响因子：
7.5
通讯作者：
Ciric, Bogoljub
中科院分区：
文献类型：
--
作者：
Hwang, Daniel;Ishikawa, Larissa Lumi Watanabe;Seyedsadr, Maryam S.;Mari, Elisabeth;Kasimoglu, Ezgi;Sahin, Ziver;Boehm, Alexandra;Jang, Soohwa;Rasouli, Javad;Vaccaro, Courtney;Gonzalez, Michael;Hakonarson, Hakon;Rostami, Abdolmohamad;Zhang, Guang-Xian;Ciric, Bogoljub
ΔdblGATA小鼠对EAE具有抗性，但不是由于它们缺乏嗜酸性粒细胞。GATA 1调节BM中HSPC的数量，ΔdblGATA突变导致炎症期间的功能缺陷。GATA结合因子1（GATA 1）是一种调控多种造血细胞谱系发育和功能的转录因子。GATA 1在造血干细胞和祖细胞（HSPC）中表达，对红系谱系定型至关重要;然而，它是否在造血干细胞（HSC）生物学和髓系细胞发育中发挥作用，以及这种作用可能是什么，目前尚不清楚。我们最初开始测试嗜酸性粒细胞在实验性自身免疫性脑脊髓炎（EAE）中的作用，EAE是一种中枢神经系统自身免疫模型，使用缺乏双GATA位点（ΔdblGATA）的小鼠，由于Gata 1的dblGATA增强子缺失而缺乏嗜酸性粒细胞，这改变了其表达。ΔdblGATA小鼠对EAE具有抗性，但不是因为缺乏嗜酸性粒细胞，这表明这些小鼠具有额外的缺陷。患有EAE的ΔdblGATA小鼠的炎性髓系细胞比对照小鼠少，表明对EAE的抵抗是由髓系细胞缺陷引起的。幼稚ΔdblGATA小鼠也显示血液中CD 11b+髓样细胞的频率降低，表明髓样细胞产生缺陷。HSPC的检查显示ΔdblGATA骨髓（BM）中的HSC和髓样细胞祖细胞较少，竞争性BM嵌合体实验显示ΔdblGATA BM重建免疫细胞的能力降低，表明Δ dblGATA HSPC数量减少导致炎症期间的功能缺陷。总之，我们的数据表明，GATA 1调节HSPC的数量，并且由于dblGATA缺失导致的GATA 1表达减少导致炎症激发后免疫应答减弱。
ΔdblGATA mice are resistant to EAE but not due to their lack of eosinophils. GATA1 regulates numbers of HSPCs in the BM, and the ΔdblGATA mutation causes a functional deficit during inflammation. GATA-binding factor 1 (GATA1) is a transcription factor that governs the development and function of multiple hematopoietic cell lineages. GATA1 is expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for erythroid lineage commitment; however, whether it plays a role in hematopoietic stem cell (HSC) biology and the development of myeloid cells, and what that role might be, remains unclear. We initially set out to test the role of eosinophils in experimental autoimmune encephalomyelitis (EAE), a model of central nervous system autoimmunity, using mice lacking a double GATA-site (ΔdblGATA), which lacks eosinophils due to the deletion of the dblGATA enhancer to Gata1, which alters its expression. ΔdblGATA mice were resistant to EAE, but not because of a lack of eosinophils, suggesting that these mice have an additional defect. ΔdblGATA mice with EAE had fewer inflammatory myeloid cells than the control mice, suggesting that resistance to EAE is caused by a defect in myeloid cells. Naïve ΔdblGATA mice also showed reduced frequency of CD11b+ myeloid cells in the blood, indicating a defect in myeloid cell production. Examination of HSPCs revealed fewer HSCs and myeloid cell progenitors in the ΔdblGATA bone marrow (BM), and competitive BM chimera experiments showed a reduced capacity of the ΔdblGATA BM to reconstitute immune cells, suggesting that reduced numbers of ΔdblGATA HSPCs cause a functional deficit during inflammation. Taken together, our data show that GATA1 regulates the number of HSPCs and that reduced GATA1 expression due to dblGATA deletion results in a diminished immune response following the inflammatory challenge.
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影响因子：
30.5
作者：
Goldmann T;Wieghofer P;Jordão MJ;Prutek F;Hagemeyer N;Frenzel K;Amann L;Staszewski O;Kierdorf K;Krueger M;Locatelli G;Hochgerner H;Zeiser R;Epelman S;Geissmann F;Priller J;Rossi FM;Bechmann I;Kerschensteiner M;Linnarsson S;Jung S;Prinz M
通讯作者：
Prinz M
DOI：
10.1073/pnas.1205858109
发表时间：
2012-09-11
影响因子：
11.1
作者：
Capotondo, Alessia;Milazzo, Rita;Biffi, Alessandra
通讯作者：
Biffi, Alessandra
影响因子：
32.4
作者：
Croxford, Andrew L.;Lanzinger, Margit;Becher, Burkhard
通讯作者：
Becher, Burkhard
影响因子：
2.6
作者：
Kozma, Gergely T.;Martelli, Fabrizio;Migliaccio, Anna Rita
通讯作者：
Migliaccio, Anna Rita
影响因子：
4.4
作者：
Barin, Jobert G.;Baldeviano, G. Christian;Cihakova, Daniela
通讯作者：
Cihakova, Daniela