Jing Chen
Program: Immunology
Current advisor: Kenneth M. Murphy, MD, PhD
Undergraduate university: New York University
Research summary
Microglia are tissue resident macrophages (TRMs) supporting CNS homeostasis that arise exclusively from the yolk sac (YS) during primitive hematopoiesis in early embryonic development. However, the genetic programs distinguishing primitive and definitive hematopoiesis remain obscure. In definitive hematopoiesis from adult hematopoietic stem cells (HSCs), macrophages arise from monocytes that require activity of the 400 bp -165 kb Zeb2 enhancer to support ZEB2 expression that is required for their development. By contrast, microglia development in primitive hematopoiesis is independent of the -165 kb Zeb2 enhancer and proceeds normally in Zeb2 -165 kb mice. Here, we identified the unique transcriptional program used by primitive hematopoiesis to support Zeb2 expression and allow microglia development. We find that co-expression of Maf and Jun can restore Zeb2 expression and development of monocytes and macrophage in HSCs from Zeb2 -165 kb mice. Further, Maf- deficient embryos have severe ablation of microglia, indicating its requirement in supporting Zeb2 during primitive hematopoiesis. Our findings demonstrate the distinct transcriptional pathways that control Zeb2 expression during primitive vs. definitive hematopoiesis..
Graduate publications
Kim S, Chen J, Ou F, Liu TT, Jo S, Gillanders WE, Murphy TL, Murphy KM. 2024 Transcription factor C/EBPα is required for the development of Ly6Chi monocytes but not Ly6Clo monocytes. Proc Natl Acad Sci USA, 121(15):e2315659121.
Ferris ST, Liu T, Chen J, Ohara RA, Ou F, Wu R, Kim S, Murphy TL, Murphy KM. 2023 WDFY4 deficiency in NOD mice ameliorates autoimmune diabetes and insulitis. Proc Natl Acad Sci USA, 120(13):e2219956120.
Kim S, Chen J, Jo S, Ou F, Ferris ST, Liu TT, Ohara RA, Anderson DA, Wu R, Chen MY, Gillanders WE, Gillanders WE, Murphy TL, Murphy KM. 2023 IL-6 selectively suppresses cDC1 specification via C/EBPβ. J Exp Med, 220(10):e20221757.
Huang X, Ferris ST, Kim S, Choudhary MNK, Belk JA, Fan C, Qi Y, Sudan R, Xia Y, Desai P, Chen J, Ly N, Shi Q, Bagadia P, Liu T, Guilliams M, Egawa T, Colonna M, Diamond MS, Murphy TL, Satpathy AT, Wang T, Murphy KM. 2021 Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis. Immunity, 54(7):1417-1432.e7.