GATA1 controls numbers of hematopoietic progenitors and their response to autoimmune neuroinflammation.

Authors

• Daniel Hwang
• Larissa Lumi Watanabe Ishikawa
• Maryam S Seyedsadr
• Elisabeth Mari
• Ezgi Kasimoglu
• Ziver Sahin
• Alexandra Boehm
• Soohwa Jang
• Javad Rasouli
• Courtney Vaccaro
• Michael Gonzalez
• Hakon Hakonarson
• Abdolmohamad Rostami
• Guang-Xian Zhang
• Bogoljub Ciric

Publication/Presentation Date

12-13-2022

Abstract

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.

Volume

6

Issue

23

First Page

5980

Last Page

5994

ISSN

2473-9537

Published In/Presented At

Hwang, D., Ishikawa, L. L. W., Seyedsadr, M. S., Mari, E., Kasimoglu, E., Sahin, Z., Boehm, A., Jang, S., Rasouli, J., Vaccaro, C., Gonzalez, M., Hakonarson, H., Rostami, A., Zhang, G. X., & Ciric, B. (2022). GATA1 controls numbers of hematopoietic progenitors and their response to autoimmune neuroinflammation. Blood advances, 6(23), 5980–5994. https://doi.org/10.1182/bloodadvances.2022008234

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

36206195

Department(s)

Administration and Leadership

Document Type

Article