The Sox Family of Transcription Factors: Versatile Regulators of Stem and Progenitor Cell Fate

Howard Hughes Medical Institute at Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
Cell stem cell (Impact Factor: 22.27). 01/2013; 12(1):15-30. DOI: 10.1016/j.stem.2012.12.007
Source: PubMed


Sox family transcription factors are well-established regulators of cell fate decisions during development. Accumulating evidence documents that they play additional roles in adult tissue homeostasis and regeneration. Remarkably, forced expression of Sox factors, in combination with other synergistic factors, reprograms differentiated cells into somatic or pluripotent stem cells. Dysregulation of Sox factors has been further implicated in diseases including cancer. Here, we review molecular and functional evidence linking Sox proteins with stem cell biology, cellular reprogramming, and disease with an emphasis on Sox2.

    • "Several transcription factors have been implicated in embryonic taste bud development. Principal among these is Sox2, which is involved in the development and maintenance of many tissues (Arnold et al., 2011; Sarkar and Hochedlinger, 2013). In mice, Sox2 is required for the differentiation of taste buds from taste papillae (Okubo et al., 2006). "
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    ABSTRACT: The sense of taste, or gustation, is mediated by taste buds, which are housed in specialized taste papillae found in a stereotyped pattern on the surface of the tongue. Each bud, regardless of its location, is a collection of ~100 cells that belong to at least five different functional classes, which transduce sweet, bitter, salt, sour and umami (the taste of glutamate) signals. Taste receptor cells harbor functional similarities to neurons but, like epithelial cells, are rapidly and continuously renewed throughout adult life. Here, I review recent advances in our understanding of how the pattern of taste buds is established in embryos and discuss the cellular and molecular mechanisms governing taste cell turnover. I also highlight how these findings aid our understanding of how and why many cancer therapies result in taste dysfunction.
    No preview · Article · Nov 2015 · Development
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    • "Sox factors in the control of stem cell identity has been highlighted by the identification of Sox2 as one of the factors originally required to reprogram differentiated cells into induced pluripotent stem cells. Aside from their roles in embryonic stem cells, cell reprogramming, and development, expression of Sox transcription factors has been found in many stem or progenitor cell populations in adult tissues, in which it is essential for the maintenance of tissue-specific stem cells and proper differentiation of progenitors (Sarkar and Hochedlinger, 2013). However, in most cases, the mechanisms regulating the function of Sox transcription factors in adult tissues remain largely unknown. "
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    ABSTRACT: Adult organs and their resident stem cells are constantly facing the challenge of adapting cell proliferation to tissue demand, particularly in response to environmental stresses. Whereas most stress-signaling pathways are conserved between progenitors and differentiated cells, stem cells have the specific ability to respond by increasing their proliferative rate, using largely unknown mechanisms. Here, we show that a member of the Sox family of transcription factors in Drosophila, Sox21a, is expressed in intestinal stem cells (ISCs) in the adult gut. Sox21a is essential for the proliferation of these cells during both normal epithelium turnover and repair. Its expression is induced in response to tissue damage, downstream of the Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways, to promote ISC proliferation. Although short-lived, Sox21a mutant flies show no developmental defects, supporting the notion that this factor is a specific regulator of adult stem cell proliferation.
    Full-text · Article · Oct 2015 · Cell Reports
    • "In particular , SOX2 is involved in the regulation of stem cell destination during embryonic development and its expression level is tightly regulated to ensure normal embryonic development [9]. SOX2 depletion by RNA interference promotes embryonic stem cell differentiation into multiple cell types [10]. SOX2 is a key factor capable of inducing pluripotency in somatic cells along with KLF4, Oct3/4, and c-Myc. "
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    ABSTRACT: Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.
    No preview · Article · Sep 2015 · International journal of clinical and experimental pathology
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