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Frontline Science: Cxxc5 expression alters cell cycle and myeloid differentiation of mouse hematopoietic stem and progenitor cells
Author(s) -
Joshi Hemant R.,
Hill Harry R.,
Zhou Zemin,
He Xiao,
Voelkerding Karl V.,
Kumánovics Attila
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.1hi0120-169r
Subject(s) - myelopoiesis , gene knockdown , progenitor cell , haematopoiesis , biology , microbiology and biotechnology , stem cell , myeloid , hematopoietic stem cell , cell cycle , progenitor , monocyte , cellular differentiation , cell , immunology , cell culture , gene , genetics
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.