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

Jung Y, Kim M, Soh H, Lee S, Kim J, Park S, Song K, Lee I - PLoS ONE (2014)

Bottom Line: The expanded population mostly consists of CD150-CD48+ cells, suggesting the expansion of lineage-restricted hematopoietic progenitor cells.Our findings indicate that TC1 is a novel hematopoietic regulator.The mechanisms of TC1-dependent HSPC regulation and lineage determination are unknown.

View Article: PubMed Central - PubMed

Affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT
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.

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Tc1 expression in bone marrow cells.(A) Confocal microscopic images of Tc1-positive cells in wild type mice bone marrow. DNA staining is done using Hoechst 33342. Relatively weak cytoplasmic staining (arrows) is present in HSC-like primitive cells (upper panel). Large progenitor cells show strong cytoplasmic staining and faint nuclear staining (arrows) (lower panel). Scale bars represent 10 µm. (B) Representative flow cytometric analysis for Tc1 and Sca-1 in total Lin− bone marrow cells (upper panels), and gated cells according to CD150/CD48 profiles (lower panels).
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pone-0100311-g004: Tc1 expression in bone marrow cells.(A) Confocal microscopic images of Tc1-positive cells in wild type mice bone marrow. DNA staining is done using Hoechst 33342. Relatively weak cytoplasmic staining (arrows) is present in HSC-like primitive cells (upper panel). Large progenitor cells show strong cytoplasmic staining and faint nuclear staining (arrows) (lower panel). Scale bars represent 10 µm. (B) Representative flow cytometric analysis for Tc1 and Sca-1 in total Lin− bone marrow cells (upper panels), and gated cells according to CD150/CD48 profiles (lower panels).

Mentions: The expression of Tc1 in wild type C57BL/6 mouse bone marrow was investigated. Previously, TC1 has been reported to express at low level in bone marrow of humans and zebrafish embryos [9], [16], while the expression in peripheral blood is too low to be detected by RNA blotting [9], [17]. Upon immunofluorescence microscopy, Tc1 was expressed in small numbers of primitive hematopoietic cells. HSC-like cells with round nuclei of 6–8 µM in diameter and scant cytoplasm showed relatively weak cytoplasmic granular staining (Figure 4A, upper panel). Large progenitor-like cells often showed strong cytoplasmic and faint nuclear staining (Figure 4A, lower panel). The nuclear translocation of TC1 upon cellular stimuli was described, suggesting a role in the regulation of downstream gene expression [19]. Cells with ring-shaped nuclei were also immunostained for Tc1 (Figure S3A, B). Myeloid cells with ring-shaped nuclei were reported in mouse but not in humans normally [24]. Differentiated myeloid cells were not immunostained (Figure S3B, C).


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

Jung Y, Kim M, Soh H, Lee S, Kim J, Park S, Song K, Lee I - PLoS ONE (2014)

Tc1 expression in bone marrow cells.(A) Confocal microscopic images of Tc1-positive cells in wild type mice bone marrow. DNA staining is done using Hoechst 33342. Relatively weak cytoplasmic staining (arrows) is present in HSC-like primitive cells (upper panel). Large progenitor cells show strong cytoplasmic staining and faint nuclear staining (arrows) (lower panel). Scale bars represent 10 µm. (B) Representative flow cytometric analysis for Tc1 and Sca-1 in total Lin− bone marrow cells (upper panels), and gated cells according to CD150/CD48 profiles (lower panels).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061086&req=5

pone-0100311-g004: Tc1 expression in bone marrow cells.(A) Confocal microscopic images of Tc1-positive cells in wild type mice bone marrow. DNA staining is done using Hoechst 33342. Relatively weak cytoplasmic staining (arrows) is present in HSC-like primitive cells (upper panel). Large progenitor cells show strong cytoplasmic staining and faint nuclear staining (arrows) (lower panel). Scale bars represent 10 µm. (B) Representative flow cytometric analysis for Tc1 and Sca-1 in total Lin− bone marrow cells (upper panels), and gated cells according to CD150/CD48 profiles (lower panels).
Mentions: The expression of Tc1 in wild type C57BL/6 mouse bone marrow was investigated. Previously, TC1 has been reported to express at low level in bone marrow of humans and zebrafish embryos [9], [16], while the expression in peripheral blood is too low to be detected by RNA blotting [9], [17]. Upon immunofluorescence microscopy, Tc1 was expressed in small numbers of primitive hematopoietic cells. HSC-like cells with round nuclei of 6–8 µM in diameter and scant cytoplasm showed relatively weak cytoplasmic granular staining (Figure 4A, upper panel). Large progenitor-like cells often showed strong cytoplasmic and faint nuclear staining (Figure 4A, lower panel). The nuclear translocation of TC1 upon cellular stimuli was described, suggesting a role in the regulation of downstream gene expression [19]. Cells with ring-shaped nuclei were also immunostained for Tc1 (Figure S3A, B). Myeloid cells with ring-shaped nuclei were reported in mouse but not in humans normally [24]. Differentiated myeloid cells were not immunostained (Figure S3B, C).

Bottom Line: The expanded population mostly consists of CD150-CD48+ cells, suggesting the expansion of lineage-restricted hematopoietic progenitor cells.Our findings indicate that TC1 is a novel hematopoietic regulator.The mechanisms of TC1-dependent HSPC regulation and lineage determination are unknown.

View Article: PubMed Central - PubMed

Affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus