Frontline Science: Cxxc5 expression alters cell cycle and myeloid differentiation of mouse hematopoietic stem and progenitor cells
| Autor: | Attila Kumánovics, Karl V. Voelkerding, Harry R. Hill, Xiao He, Hemant R. Joshi, Zemin Zhou |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Myeloid Immunology Bone Marrow Cells Mice Transgenic Biology Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Immunology and Allergy Myeloid Cells Progenitor cell Alleles Myelopoiesis Gene knockdown Gene Expression Profiling Monocyte Cell Cycle Gene Expression Regulation Developmental High-Throughput Nucleotide Sequencing Hematopoietic stem cell Cell Differentiation Cell Biology Cell cycle Flow Cytometry Hematopoietic Stem Cells Cell biology DNA-Binding Proteins Haematopoiesis 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Transcription Factors |
| Zdroj: | Journal of Leukocyte Biology. 108:469-484 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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