Maintenance of hematopoietic stem and progenitor cells in fetal intra-aortic hematopoietic clusters by the Sox17-Notch1-Hes1 axis

Saito, Kosuke; Nobuhisa, Ikuo; Harada, Kaho; Takahashi, Satoshi; Anani, Maha; Lickert, Heiko; Kanai‐Azuma, Masami; Kanai, Yoshikatsu; Taga, Tetsuya

doi:10.1016/j.yexcr.2018.02.014

Cited by 8 publications

(15 citation statements)

References 47 publications

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“…The critical role of SOX17 in HSC development has been widely recognized (Clarke et al, 2013;Kim et al, 2007;Lizama et al, 2015;Nobuhisa et al, 2014;Saito et al, 2018). Although SOX17 regulates multiple steps along the HSC developmental path, including HE specification, EHT, and HSC maintenance and expansion, the stage-specific molecular mechanisms of SOX17 are not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…Sox17 has been found to be expressed in the arterial vasculature (Liao et al, 2009) and the hemogenic endothelium (HE) in the aorta-gonad-mesonephros (AGM) region (Clarke et al, 2013;Corada et al, 2013), in which it is required for arterial specification (Corada et al, 2013) and essential for establishing the definitive, but not primitive, hematopoietic program (Clarke et al, 2013) within the murine embryo. Although Sox17 actively prevents endothelial-to-hematopoietic transition (EHT) by repressing Runx1 (Lizama et al, 2015), Sox17 remains critical for maintaining intra-aortic hematopoietic clusters (IAHCs) and fetal liver hematopoietic stem cells (HSCs) (Kim et al, 2007;Nobuhisa et al, 2014;Saito et al, 2018). Transduction of human embryonic stem cell (hESC)-derived CD34 + HE/OP9 cocultures with a tamoxifen-inducible murine Sox17 transgene revealed that tamoxifen treatment expands CD34 + CD43 + CD45 À/low cells coexpressing the endothelial marker VE-cadherin (VEC) (Nakajima-Takagi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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SOX17 integrates HOXA and arterial programs in hemogenic endothelium to drive definitive lympho-myeloid hematopoiesis

et al. 2021

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SUMMARY SOX17 has been implicated in arterial specification and the maintenance of hematopoietic stem cells (HSCs) in the murine embryo. However, knowledge about molecular pathways and stage-specific effects of SOX17 in humans remains limited. Here, using SOX17-knockout and SOX17-inducible human pluripotent stem cells (hPSCs), paired with molecular profiling studies, we reveal that SOX17 is a master regulator of HOXA and arterial programs in hemogenic endothelium (HE) and is required for the specification of HE with robust lympho-myeloid potential and DLL4 + CXCR4 + phenotype resembling arterial HE at the sites of HSC emergence. Along with the activation of NOTCH signaling, SOX17 directly activates CDX2 expression, leading to the upregulation of the HOXA cluster genes. Since deficiencies in HOXA and NOTCH signaling contribute to the impaired in vivo engraftment of hPSC-derived hematopoietic cells, the identification of SOX17 as a key regulator linking arterial and HOXA programs in HE may help to program HSC fate from hPSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SOX17 integrates HOXA and arterial programs in hemogenic endothelium to drive definitive lympho-myeloid hematopoiesis

et al. 2021

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“…The first long-term regenerated HSCs are detected in the AGM region. By positively regulating Notch1 through the transcription factor SOX17, Saito et al ( 35 ) revealed that Notch1 intracellular domain (N1ICD) or its downstream target protein Hes1 transduced HSCs to maintain the ability of multipotent colony formation in AGM. By contrast, Notch1 and Hes1 gene knockout resulted in a decrease in the ability to form multipotent colonies.…”

Section: Notch1 and Hscsmentioning

confidence: 99%

Fate of hematopoietic stem cells determined by Notch1 signaling (Review)

Wang

Zhang

et al. 2021

Exp Ther Med

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Regulation of the fate of hematopoietic stem cells (HSCs), including silencing, self-renewal or differentiation into blood line cells, is crucial to maintain the homeostasis of the human blood system and prevent leukemia. Notch1, a key receptor in the Notch signaling pathway, plays an important regulatory role in these properties of HSCs, particularly in the maintenance of the stemness of HSCs. In recent decades, the ubiquitination modification of Notch1 has been gradually revealed, and also demonstrated to affect the proliferation and differentiation of HSCs. Therefore, a detailed elucidation of Notch1 and its ubiquitination modification may help to improve understanding of the maintenance of HSC properties and the pathogenesis of leukemia. In addition, it may aid in identifying potential therapeutic targets for specific leukemias and provide potential prognostic indicators for HSC transplantation (HSCT). In the present review, the association between Notch1 and HSCs and the link between the ubiquitination modification of Notch1 and HSCs were described. In addition, the association between abnormal HSCs mediated by Notch1 or ubiquitinated Notch1and T-cell acute lymphoblastic leukemia (T-ALL) was also examined, which provides a promising direction for clinical application.

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“…This suggests that hematopoietic cells that emerge from hemogenic endothelia are differentiated and matured in IAHCs. Sox17 is found to be expressed in cells located in the vessel wall side of IAHCs as assessed by in situ hybridization and whole-mount immunohistochemistry [57][58][59]. Researchers have attempted to isolate cells from IAHCs, which contain HSPCs, and have performed the transplantation experiments.…”

Section: Involvement Of Sox17 In Midgestational Hematopoiesismentioning

confidence: 99%

“…Notch1, Notch4, and the Notch ligand, Delta-like ligand 4, is expressed in endothelial cells of dorsal aorta as well as IAHCs [64]. Sox17 directly induces the expression of the Notch1 gene and the Notch1-downstream molecule Hes1, and the Sox17-Notch1-Hes1 axis is important for the maintenance of the hematopoietic activity in Sox17-transduced cells A B [59]. Furthermore, adherent molecules, such as endothelial cell-selective adhesion molecules (ESAM) and VE-cad directly induced by Sox17, are required for the formation of the cell cluster with the hematopoietic ability in Sox17-transduced cells [65].…”

Section: Involvement Of Sox17 In Midgestational Hematopoiesismentioning

confidence: 99%

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

2020

Self Cite

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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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Maintenance of hematopoietic stem and progenitor cells in fetal intra-aortic hematopoietic clusters by the Sox17-Notch1-Hes1 axis

Cited by 8 publications

References 47 publications

SOX17 integrates HOXA and arterial programs in hemogenic endothelium to drive definitive lympho-myeloid hematopoiesis

SOX17 integrates HOXA and arterial programs in hemogenic endothelium to drive definitive lympho-myeloid hematopoiesis

Fate of hematopoietic stem cells determined by Notch1 signaling (Review)

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

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