Sox17 as a candidate regulator of myeloid restricted differentiation potential

Anani, Maha; Nobuhisa, Ikuo; Osawa, Mitsujiro; Iwama, Atsushi; Harada, Kaho; Saito, Kosuke; Taga, Tetsuya

doi:10.1111/dgd.12147

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…2A) [73]. Three populations of progenitors are observed in an in vitro culture system in which Sox17-transduced cells are co-cultured with OP9 stromal cells and Sox17-CMPs are maintained at least after five passages [73]. These results indicate that sustained expression of Sox17 in HSPCs and cells from IAHCs provokes the leukemia-like abnormalities, and the recipient mice finally die.…”

Section: Leukemia-like Abnormalities Of Sox17-sustained Expression Inmentioning

confidence: 93%

“…When Sox17-transduced IAHCs are transplanted into irradiated mice, the absolute number of Sox17-transduced-CMPs (Sox17-CMPs) aberrantly increased to a greater extent than that of Sox17-transduced-GMPs (Sox17-GMPs) and Sox17-transduced-MEPs (Sox17-MEPs; see the "transplantation" part of Fig. 2A) [73]. Three populations of progenitors are observed in an in vitro culture system in which Sox17-transduced cells are co-cultured with OP9 stromal cells and Sox17-CMPs are maintained at least after five passages [73].…”

Section: Leukemia-like Abnormalities Of Sox17-sustained Expression Inmentioning

confidence: 99%

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Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway

2020

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A transcription factor Sry-related high mobility group box (Sox) 17 is involved in developmental processes including spermatogenesis, cardiovascular system, endoderm formation, and so on. In this article, we firstly review the studies on the relation between the Sox17 expression and tumor malignancy. Although Sox17 positively promotes various tissue development, most of the cancers associated with Sox17 show decreased expression levels of Sox17, and an inverse correlation between Sox17 expression and malignancy is revealed. We briefly discuss the mechanism of such Sox17 down-regulation by focusing on DNA methylation of CpG sites located in the Sox17 gene promoter. Next, we overview the function of Sox17 in the fetal hematopoiesis, particularly in the dorsal aorta in midgestation mouse embryos. The Sox17 expression in hematopoietic stem cell (HSC)-containing intra-aortic hematopoietic cell cluster (IAHCs) is important for the cluster formation with the hematopoietic ability. The sustained expression of Sox17 in adult bone marrow HSCs and the cells in IAHCs of the dorsal aorta indicate abnormalities that are low lymphocyte chimerism and the aberrant proliferation of common myeloid progenitors in transplantation experiments. We then summarize the perspectives of Sox17 research in cancer control.

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Section: Leukemia-like Abnormalities Of Sox17-sustained Expression Inmentioning

confidence: 93%

Section: Leukemia-like Abnormalities Of Sox17-sustained Expression Inmentioning

confidence: 99%

Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway

2020

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“…Similarly, in E10.5 aorta-derived haematopoietic clusters, the enforced expression of SOXF factors, and SOX17 in particular, resulted in the maintenance and expansion of blood progenitors and HSCs [ 17 ]. A role for SOX17 in promoting the myeloid specification of E10.5 blood progenitors was also suggested in follow-up studies [ 19 ]. Our group showed that Sox7 expression was upregulated in mesoderm precursors at the onset of blood specification and downregulated as differentiation progresses to committed blood lineages [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 95%

SOX7-enforced expression promotes the expansion of adult blood progenitors and blocks B-cell development

2016

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During embryogenesis, the three SOXF transcription factors, SOX7, SOX17 and SOX18, regulate the specification of the cardiovascular system and are also involved in the development of haematopoiesis. The ectopic expression of SOX17 in both embryonic and adult blood cells enhances self-renewal. Likewise, the enforced expression of SOX7 during embryonic development promotes the proliferation of early blood progenitors and blocks lineage commitment. However, whether SOX7 expression can also affect the self-renewal of adult blood progenitors has never been explored. In this study, we demonstrate using an inducible transgenic mouse model that the enforced expression of Sox7 ex vivo in bone marrow/stroma cell co-culture promotes the proliferation of blood progenitors which retain multi-lineage short-term engrafting capacity. Furthermore, SOX7 expression induces a profound block in the generation of B lymphocytes. Correspondingly, the ectopic expression of SOX7 in vivo results in dramatic alterations of the haematopoietic system, inducing the proliferation of blood progenitors in the bone marrow while blocking B lymphopoiesis. In addition, SOX7 expression induces extra-medullary haematopoiesis in the spleen and liver. Together, these data demonstrate that the uncontrolled expression of the transcription factor SOX7 in adult haematopoietic cells has dramatic consequences on blood homeostasis.

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“…Up until now, we have shown that the introduction of Sox17 in IAHC cells in the AGM region results in the formation of cell clusters with hematopoietic potential [ 10 , 17 , 23 – 25 ] and assume that Sox17 induces the expression of target genes to maintain an undifferentiated state via the interaction of Sox17 with its promoter. Such genes include Notch1 [ 17 ], ESAM, and VE-Cad [ 23 ], and each gene induced by Sox17 may have distinct functions in the maintenance of undifferentiated states.…”

Section: Introductionmentioning

confidence: 99%

A Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo

et al. 2023

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Background During mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aorta’s intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17 is expressed in IAHCs, and that, among them, CD45lowc-Kithigh cells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity. Methods RNA-sequencing (RNA-seq) analysis was done to identify genes that are upregulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study, and firstly, the whole-mount immunostaining was done. We conducted luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay to examine whether Sox17 regulates Rasip1 gene expression via binding to its enhancer element. We also analyzed the cluster formation and the multilineage colony-forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells. Results The increase of the Rasip1 expression level was observed in Sox17-positive CD45lowc-Kithigh cells as compared with the Sox17-nonexpressing control. Also, the expression level of the Rasip1 gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Rasip1 expression was observed in most part of c-Kit+Sox17+ cells in IAHCs. Luciferase reporter assay and ChIP assay indicated that one of the five putative Sox17-binding sites in the Rasip1 enhancer region was important for Rasip1 expression via Sox17 binding. Rasip1 knockdown in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability, while overexpression of Rasip1 in CD45lowc-Kithigh cells led to a significant but transient increase in hematopoietic activity. Conclusions Rasip1 knockdown in Sox17-transduced CD45lowc-Kithigh cells displayed a significant decrease in the multilineage colony-forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45lowc-Kithigh cells led to a significant but transient increase in the multilineage colony-forming ability, suggesting the presence of a cooperating factor for sustained hematopoietic activity.

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Sox17 as a candidate regulator of myeloid restricted differentiation potential

Cited by 5 publications

References 30 publications

Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway

Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway

SOX7-enforced expression promotes the expansion of adult blood progenitors and blocks B-cell development

A Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo

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