TC1(C8orf4) regulates hematopoietic stem/progenitor cells and hematopoiesis

• Published in: PloS one Vol. 9; no. 6; p. e100311
• Main Authors: Jung, Yusun, Kim, Minsung, Soh, Hyunsu, Lee, Soyoung, Kim, Jungtae, Park, Surim, Song, Kyuyoung, Lee, Inchul
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-06-2014; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Blood; Blood cells; Blotting, Western; Bone marrow; Bone Marrow - metabolism; Bone Marrow - pathology; c-Kit protein; CD150 antigen; Cell Differentiation; Cell Lineage; Cells (biology); Cells, Cultured; Consortia; Cytokines; Erythrocytes; Female; Flow Cytometry; Genomes; Hematology; Hematopoiesis; Hematopoiesis - physiology; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; HL-60 Cells; Humans; Immunoenzyme Techniques; Inflammation; Life sciences; Lymphoid cells; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence; Neoplasm Proteins - physiology; Parkinson's disease; Peripheral blood; Progenitor cells; PU.1 protein; Real-Time Polymerase Chain Reaction; Regulators; Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Stem cells; Transcription
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100311

Hematopoiesis is a complex process requiring multiple regulators for hematopoietic stem/progenitor cells (HSPC) and differentiation to multi-lineage blood cells. TC1(C8orf4) is implicated in cancers, hematological malignancies and inflammatory activation. Here, we report that Tc1 regulates hematopoiesis in mice. Myeloid and lymphoid cells are increased markedly in peripheral blood of Tc1-deleted mice compared to wild type controls. Red blood cells are small-sized but increased in number. The bone marrow of Tc1-/- mice is normocellular histologically. However, Lin-Sca-1+c-Kit+ (LSK) cells are expanded in Tc1-/- mice compared to wild type controls. The expanded population mostly consists of CD150-CD48+ cells, suggesting the expansion of lineage-restricted hematopoietic progenitor cells. Colony forming units (CFU) are increased in Tc1-/- mice bone marrow cells compared to controls. In wild type mice bone marrow, Tc1 is expressed in a limited population of HSPC but not in differentiated cells. Major myeloid transcriptional regulators such as Pu.1 and Cebpα are not up-regulated in Tc1-/- mice bone marrow. Our findings indicate that TC1 is a novel hematopoietic regulator. The mechanisms of TC1-dependent HSPC regulation and lineage determination are unknown.