Early Growth Response Gene-2 (Egr-2) Regulates the Development of B and T Cells

Abstract

BackgroundUnderstanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development.Methods and FindingsThe expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow.ConclusionsOur results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.

Acquired Initiating Mutations in Early Hematopoietic Cells of CLL Patients

“…The EGR2 gene encodes a versatile transcription factor that participates in the control of cellular differentiation, including myeloid (23), B-lymphoid, and T-lymphoid differentiation (24,25). All EGR2 mutations identified in CLL were heterozygous missense mutations, and, with the exception of R426Q, were located within the zinc-finger domains (Fig.…”

“…EGR2 is a downstream target of the BCR and pre-BCR complexes, through an intracellular signaling cascade involving BRAF, ERK, ELK-SRF, and finally upregulation of EGR2 transcription (19). EGR2 plays an important role in the fine-tuning of early B-cell differentiation (19,24,36,37). Expression of a CLL BRAF mutant in murine progenitors induced abnormal B-cell maturation in mice, including low expression of IgM, a feature of human CLL.…”

TLR9 ligation in pancreatic stellate cells promotes tumorigenesis

“…qPCR was performed using the RT 2 SYBR Green qPCR Mastermix (QIA GEN) on the Stratagene MX3005P (Stratagene). The following forward (F) and reverse (R) primers were used: F, 5′-AAT CGTGC GTGAC ATCAA AG-3′ and R, 5′-ATG CCACA GGATT CCATA CC-3′ for mouse β-actin (Li et al, 2011); F, 5′-GTA CCATG ACACT CTGCA ACC-3′ and R, 5′-GTC AGGAA AATGA CACCT GGC-3′ for mouse Ccl3 (Volat et al, 2012); F, 5′-TGG GATGC CTTTG TGGAA CT-3′ and R, 5′-ACA GCCAG GAGAA ATCAA ACAG-3′ for mouse Bcl2 (Mohrin et al, 2010); F, 5′-GGC TGGGA CACTT TTGTG GAT-3′ and R, 5′-GCG CTCCT GGCCT TTCC-3′ for mouse Bcl2l1 (Bcl-xL; Mohrin et al, 2010); F, 5′-GGA CCTCG AGTGT GAAGC AT-3′ and R, CTG GAGCT CACAG GGTAG GA-3′ for human Tlr9; F, 5′-CTG TGGCA TCCAC GAAAC TA-3′ and R, 5′-AGT ACTTG CGCTC AGGAG GA-3′ for human β-actin (Ho-Pun-Cheung et al, 2009). For mouse Ccl11, predesigned primers were purchased from QIA GEN.…”

Direct Conversion of Cord Blood CD34+ Cells Into Neural Stem Cells by OCT4

“…The original CB CD34+ cells did not express any of the all midbrain and forebrain markers tested and were negative for hindbrain GBX1 as well. Notably, CB cells are positive for EGR2, HOXA2, HOXB2, and HOXB6 makers because they are also related to adult hematopoiesis [16,17]. To check whether the CB-iNSCs could be induced for midbrain neuron commitment, we induced these CB-iNSCs in specific medium condition for midbrain dopaminergic neuron differentiation.…”