Dataset Information

Trp53 regulates platelets in bone marrow via the PI3K pathway.

ABSTRACT: The p53 gene is well known as a key tumor suppressor gene; it is vital for hematopoietic stem cell differentiation and growth. In the present study, the change of platelets (PLTs) in p53 knockout mice (p53-/- mice) was investigated. The peripheral blood cell subsets and PLT parameters in p53-/-mice were compared with those in age-matched p53+/+ mice. Bleeding time as well as the alteration of PLT levels, were analyzed with the PLT marker CD41 antibody using flow cytometry. The results revealed that the number of PLTs in p53-/- mice was significantly lower than that in p53+/+ mice. Bleeding time was prolonged in the peripheral blood of p53-/- mice compared with that of p53+/+ mice. Furthermore, the related gene expression of the PI3K signaling pathway in the bone marrow of p53-/- mice was shown to be associated with plateletogenesis. PI3K inhibitor (LY294002) was also used to treat p53-/- mice, and the results demonstrated that LY294002 revert the change of PLTs in these mice. In summary, PLTs were altered in p53-/- mice, and the PI3K signaling pathway was involved in that process, suggesting that the p53-dependent PI3K signaling pathway is involved in thrombocytopenia or PLT diseases. PLT number is reduced in p53 deficiency; however, this reduction could be reverted by inhibiting the PI3K pathway.

SUBMITTER: Yang M

PROVIDER: S-EPMC7388439 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trp53 regulates platelets in bone marrow via the PI3K pathway.

Yang Mingming M Liu Qing Q Niu Ting T Kuang Jianbiao J Zhang Xiaohan X Jiang Lingbi L Li Siqi S He Xiaodong X Wang Lijing L Li Jiangchao J

Experimental and therapeutic medicine 20200609 2

The p53 gene is well known as a key tumor suppressor gene; it is vital for hematopoietic stem cell differentiation and growth. In the present study, the change of platelets (PLTs) in p53 knockout mice (p53-/- mice) was investigated. The peripheral blood cell subsets and PLT parameters in p53-/-mice were compared with those in age-matched p53+/+ mice. Bleeding time as well as the alteration of PLT levels, were analyzed with the PLT marker CD41 antibody using flow ...[more]

PMID: 32765666

Similar Datasets

Project description:Platelets are essential for hemostatic plug formation and thrombosis. The mechanisms of megakaryocyte (MK) differentiation and subsequent platelet production from stem cells remain only partially understood. The manufacture of megakaryocytes (MKs) and platelets from cell sources including hematopoietic stem cells and pluripotent stem cells have been highlighted for studying the platelet production mechanisms as well as for the development of new strategies for platelet transfusion. The mouse bone marrow stroma cell line OP9 has been widely used as feeder cells for the differentiation of stem cells into MK lineages. OP9 cells are reported to be pre-adipocytes. We previously reported that 3T3-L1 pre-adipocytes differentiated into MKs and platelets. In the present study, we examined whether OP9 cells differentiate into MKs and platelets using MK lineage induction (MKLI) medium previously established to generate MKs and platelets from hematopoietic stem cells, embryonic stem cells, and pre-adipocytes. OP9 cells cultured in MKLI medium had megakaryocytic features, i.e., positivity for surface markers CD41 and CD42b, polyploidy, and distinct morphology. The OP9-derived platelets had functional characteristics, providing the first evidence for the differentiation of OP9 cells into MKs and platelets. We then analyzed gene expressions of critical factors that regulate megakaryopoiesis and thrombopoiesis. The gene expressions of p45NF-E2, FOG, Fli1, GATA2, RUNX1, thrombopoietin, and c-mpl were observed during the MK differentiation. Among the observed transcription factors of MK lineages, p45NF-E2 expression was increased during differentiation. We further studied MK and platelet generation using p45NF-E2-overexpressing OP9 cells. OP9 cells transfected with p45NF-E2 had enhanced production of MKs and platelets. Our findings revealed that OP9 cells differentiated into MKs and platelets in vitro. OP9 cells have critical factors for megakaryopoiesis and thrombopoiesis, which might be involved in a mechanism of this differentiation. p45NF-E2 might also play important roles in the differentiation of OP9 cells into MK lineages cells.

Dataset Information

Trp53 regulates platelets in bone marrow via the PI3K pathway.

Publications

Trp53 regulates platelets in bone marrow via the PI3K pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets