He, Xiao

MHC Class II molecules are essential in antigen presentation and selection of the CD4+ T cell repertoire. They are mainly expressed on professional Antigen Presenting Cells (APC), i.e. B lymphocytes, dendritic cells and macrophages. Activated human T lymphocytes also express MHC Class II but MHC Class II expression is not detected on activated mouse T cells. HLA‐DR3 can be expressed as a transgene on CD4+ T cells in complete MHC Class II knock‐out (AEo) mice, but not in I‐Ab knock‐out (Abo) mice, suggesting that a gene, which could modify the expression of HLA‐DR3, might exist between I‐A and I‐E. Expression sequence tag (EST) databases were searched using the flank regions between I‐A and I‐E and a new potential gene was identified. No similar sequence was found in the human genome database. Expression in multiple mouse tissues, but not in human cell lines, was verified by RT‐PCR. However, this gene was found to be expressed in B6 mouse B cells and two mouse B cell lines, but not in T cells, indicating that it might not be related to the expression of HLA‐DR3. Transduction of this gene into the LG2 cell line had no effect on MHC II expression. In summary, we report the discovery of a new gene between the I‐Aa and I‐Eb1 region in C57BL/6 mice and its function remains unknown. (Supported by NIH‐AI30554)

Abstract CXXC5 is a member of the CXXC-type zinc finger epigenetic regulators. Various hematopoietic and nonhematopoietic roles have been assigned to CXXC5. In the present study, the role of Cxxc5 in myelopoiesis was studied using overexpression and short hairpin RNA-mediated knockdown in mouse early stem and progenitor cells defined as Lineage− Sca-1+c-Kit+ (LSK) cells. Knockdown of Cxxc5 in mouse progenitor cells reduced monocyte and increased granulocyte development in ex vivo culture systems. In addition, ex vivo differentiation and proliferation experiments demonstrated that the expression of Cxxc5 affects the cell cycle in stem/progenitor cells and myeloid cells. Flow cytometry-based analyses revealed that down-regulation of Cxxc5 leads to an increase in the percentage of cells in the S phase, whereas overexpression results in a decrease in the percentage of cells in the S phase. Progenitor cells proliferate more after Cxxc5 knockdown, and RNA sequencing of LSK cells, and single-cell RNA sequencing of differentiating myeloid cells showed up-regulation of genes involved in the regulation of cell cycle after Cxxc5 knockdown. These results provide novel insights into the physiologic function of Cxxc5 during hematopoiesis, and demonstrate for the first time that it plays a role in monocyte development.