The Satb1 Protein Directs Hematopoietic Stem Cell Differentiation toward Lymphoid Lineages

Satoh, Yusuke; Yokota, Takafumi; Sudo, Takao; Kondo, Motonari; Lai, Anne Y.; Kincade, Paul W.; Kouro, Taku; Iida, Ryuji; Kokame, Koichi; Miyata, Toshiyuki; Habuchi, Yoko; Matsui, Kunihiko; Tanaka, Hirokazu; Matsumura, Itaru; Oritani, Kenji; Kohwi‐Shigematsu, Terumi; Kanakura, Yuzuru

doi:10.1016/j.immuni.2013.05.014

Cited by 99 publications

(99 citation statements)

References 41 publications

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“…SATB1 forms complexes with SWI/SNF factors and positively and negatively regulates the expression of a vast number of genes (28)(29)(30). SATB1 expression is observed in hematopoietic stem cells (HSCs), and its expression is abundant in thymocytes (31,32). Accordingly, SATB1 and its target genes are involved in various cellular functions in different types of blood cells.…”

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SATB1 Plays a Critical Role in Establishment of Immune Tolerance

Kondo

Tanaka

Kuwabara

et al. 2016

The Journal of Immunology

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Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that is expressed by T cells. T cell development is severely impaired in SATB1 null mice; however, because SATB1 null mice die by 3 wk of age, the roles of SATB1 in T cell development have not been well clarified. In this study, we generated and analyzed SATB1 conditional knockout (cKO) mice, in which the SATB1 gene was deleted from all hematopoietic cells. T cell numbers were reduced in these mice, mainly because of a deficiency in positive selection at the CD4+CD8+ double-positive stage during T cell development in the thymus. We also found that SATB1 cKO mice developed autoimmune diseases within 16 wk after birth. In SATB1 cKO mice, the numbers of Foxp3+ regulatory T (Treg) cells were significantly reduced at 2 wk of age compared with wild-type littermates. Although the numbers gradually increased upon aging, Treg cells in SATB1 cKO mice were still less than those in wild-type littermates at adulthood. Suppressive functions of Treg cells, which play a major role in establishment of peripheral tolerance, were also affected in the absence of SATB1. In addition, negative selection during T cell development in the thymus was severely impaired in SATB1 deficient mice. These results suggest that SATB1 plays an essential role in establishment of immune tolerance.

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“…For example, it has been demonstrated that SATB1 is necessary for the self-renewal of HSC (32). SATB1 also plays a role in lymphoid lineage specification and/or commitment (31). In SATB1 null mice, however, a dramatic change in cell phenotype is observed in the thymus, where T cell development is mostly stagnated at the DP stage (30).…”

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confidence: 99%

SATB1 Plays a Critical Role in Establishment of Immune Tolerance

Kondo

Tanaka

Kuwabara

et al. 2016

The Journal of Immunology

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“…However, so far, no cases of obvious cell fate conversion have been reported in mice with genetically modified polycomb components. This is also true for other epigenetic modulators, such as DNA methyltransferase (Trowbridge et al 2009;Challen et al 2014) or AT-rich sequence binding 1 (Satb1) (Satoh et al 2013;Will et al 2013).…”

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Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program

et al. 2016

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In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5. These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program.

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“…Until recently, the majority of reports on SATB1 and SATB2 were limited to roles in development of the immune and nervous systems, respectively, 22,23 and roles for SATB proteins in cancer had not been well described. Han et al 6 demonstrated that SATB1 is highly expressed in aggressive breast tumors and reprograms gene expression to promote growth and metastases.…”

Section: Discussionmentioning

confidence: 99%

SATB2 enhances migration and invasion in osteosarcoma by regulating genes involved in cytoskeletal organization

et al. 2014

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Osteosarcoma (OS) is the most common malignant bone tumor and the majority of recurrences are due to metastasis. However, the molecular mechanisms that regulate OS metastatic spread are largely unknown. In this study, we report that special AT-rich-binding protein 2 (SATB2) is highly expressed in OS cells and tumors. Short hairpin RNA-mediated knockdown of SATB2 (sh-SATB2) decreases migration and invasion of OS cells without affecting proliferation or viability. Microarray analysis identified genes that were differentially regulated by SATB2 including the actin-binding protein Epithelial Protein Lost In Neoplasm (EPLIN), which was upregulated in sh-SATB2 cells. Silencing EPLIN rescues the decreased invasion observed in sh-SATB2 cells. Pathway analyses of SATB2-regulated genes revealed enrichment of those involved in cytoskeleton dynamics, and increased stress fiber formation was detected in cells with SATB2 knockdown. Furthermore, sh-SATB2 cells exhibit increased RhoA, decreased Rac1 and increased phosphorylation of focal adhesion kinase (FAK) and paxillin. These findings identify SATB2 as a novel regulator of OS invasion, in part via effects on EPLIN and the cytoskeleton.

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The Satb1 Protein Directs Hematopoietic Stem Cell Differentiation toward Lymphoid Lineages

Cited by 99 publications

References 41 publications

SATB1 Plays a Critical Role in Establishment of Immune Tolerance

SATB1 Plays a Critical Role in Establishment of Immune Tolerance

Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program

SATB2 enhances migration and invasion in osteosarcoma by regulating genes involved in cytoskeletal organization

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