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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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Related in: MedlinePlus

Tc1-targeting strategy.Restriction maps of wild type allele, targeting construct and targeted allele. The probe used for Southern blot analysis is indicated. The top line represents the structure and partial restriction map from wild-type allele of Tc1. The middle and low lines depict the targeting construct and predicted structure of targeted allele, respectively.
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pone-0100311-g001: Tc1-targeting strategy.Restriction maps of wild type allele, targeting construct and targeted allele. The probe used for Southern blot analysis is indicated. The top line represents the structure and partial restriction map from wild-type allele of Tc1. The middle and low lines depict the targeting construct and predicted structure of targeted allele, respectively.

Mentions: Tc1-targeted mice were generated (Figure 1 and Figure S1), and were back-crossed to C57BL/6 mice for 10 generations. Systemic deletion in homozygotes was confirmed by RT-PCR (Figure S2) and western blotting (data not shown). Tc1-deleted homozygotes have thrived under the SPF environment. Interestingly, the hematological profile changed remarkably.


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-targeting strategy.Restriction maps of wild type allele, targeting construct and targeted allele. The probe used for Southern blot analysis is indicated. The top line represents the structure and partial restriction map from wild-type allele of Tc1. The middle and low lines depict the targeting construct and predicted structure of targeted allele, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0100311-g001: Tc1-targeting strategy.Restriction maps of wild type allele, targeting construct and targeted allele. The probe used for Southern blot analysis is indicated. The top line represents the structure and partial restriction map from wild-type allele of Tc1. The middle and low lines depict the targeting construct and predicted structure of targeted allele, respectively.
Mentions: Tc1-targeted mice were generated (Figure 1 and Figure S1), and were back-crossed to C57BL/6 mice for 10 generations. Systemic deletion in homozygotes was confirmed by RT-PCR (Figure S2) and western blotting (data not shown). Tc1-deleted homozygotes have thrived under the SPF environment. Interestingly, the hematological profile changed remarkably.

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