GATA1 Controls Numbers of Hematopoietic Progenitors and Their Response to Autoimmune Neuroinflammation
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.
Hwang, Daniel; Ishikawa, Larissa; Seyedsadr, Maryam S.; Mari, Elisabeth R.; Kasimoglu, Ezgi; Sahin, Ziver; Boehm, Alexandra; Jang, Soohwa; Rasouli, Javad; Vaccaro, Courtney; Gonzalez, Michael; Hakonarson, Hakon; Rostami, Mohamad; Zhang, Guang-Xian; and Ciric, Bogoljub, "GATA1 Controls Numbers of Hematopoietic Progenitors and Their Response to Autoimmune Neuroinflammation" (2022). Department of Neurology Faculty Papers. Paper 307.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
This article is the author’s final published version in Blood Advances, Volume 6, Issue 23, December 2022, Pages 5980-5994.
The published version is available at https://doi.org/10.1182/bloodadvances.2022008234. Copyright © The American Society of Hematology.
Publication made possible in part by support from the Jefferson Open Access Fund