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.

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    • "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.
    Development 11/2015; 142(21):3620-3629. DOI:10.1242/dev.120394 · 6.46 Impact Factor
    • "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.
    International journal of clinical and experimental pathology 09/2015; 8(7):8189-98. · 1.89 Impact Factor
    • "Sox2 and Sox3 are members of the SoxB1 family of SRY-related transcription factors. Sox2 is expressed in early stages in the developing nervous system, in neural stem and progenitor cells and in most epidermal and ectodermal stem cells (Kamachi and Kondoh, 2013; Sarkar and Hochedlinger, 2013). Sox2 also plays a key role in early development, nervous system development, pluripotency of stem cell biology, reprogramming, adult neurogenesis and tissue homeostasis (Avilion et al., 2003; Ellis et al., 2004; Ferri et al., 2004; Masui et al., 2007; Pevny and Nicolis, 2010; Arnold et al., 2011; Kamachi and Kondoh, 2013; Thomson et al., 2011). "
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    ABSTRACT: Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2(/)3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2(/)3(+) cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2(/)3(+) neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. Copyright © 2015. Published by Elsevier Inc.
    Developmental Biology 03/2015; DOI:10.1016/j.ydbio.2015.03.009 · 3.55 Impact Factor
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