From stem cells to neurons and glia: a Soxist's view of neural development

Wegner, Michael; Stolt, C. Claus

doi:10.1016/j.tins.2005.08.008

Cited by 384 publications

(359 citation statements)

References 68 publications

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“…However, SOX2 expression can still provide useful insight when considered in the context of other markers such as TUJ1 and nestin. The observed pattern of nestin and SOX2 expression is consistent with the expectation that the transient expression of nestin decreases [47] and that the overall proportion of undifferentiated cells expressing SOX2 decreases [48] as the cells specialize down neuronal lineages. Interestingly, for the ESC-derived EBs, the observed decreases in nestin and SOX2 expression over this time period were not significant.…”

Section: 23supporting

confidence: 87%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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Induced pluripotent stem cells (iPSCs) are generated from adult somatic cells through the induction of key transcription factors that restore the ability to become any cell type found in the body. These cells are of interest for tissue engineering due to their potential for developing patient-specific therapies. As the technology for generating iPSCs advances, it is important to concurrently investigate protocols for the efficient differentiation of these cells to desired downstream phenotypes in combination with biomaterial scaffolds as a way of engineering neural tissue. For such applications, the generation of neurons within three dimensional fibrin scaffolds has been well characterized as a cell-delivery platform for murine embryonic stem cells (ESCs) but has not yet been applied to murine iPSCs. Given that iPSCs have been reported to differentiate less effectively than ESCs, a key objective of this investigation is to maximize the proportion of iPSC-derived neurons in fibrin through the choice of differentiation protocol. To this end, this study compares two EB-mediated protocols for generating neurons from murine iPSCs and ESCs: an 8-day 4-/4+ protocol using soluble retinoic acid in the last 4 days and a 6-day 2-/4+ protocol using soluble retinoic acid and the small molecule sonic hedgehog agonist purmorphamine in the last 4 days. EBs were then seeded in fibrin scaffolds for 14 days to allow further differentiation into neurons. EBs generated by the 2-/4+ protocol yielded a higher percentage of neurons compared to those from the 4-/4+ protocol for both iPSCs and ESCs. The results demonstrate the successful translation of the fibrin-based cell-delivery platform for use with murine iPSCs and furthermore that the proportion of neurons generated from murine iPSC-derived EBs seeded in fibrin can be maximized using the 2-/4+ differentiation protocol. Together, these findings validate the further exploration of 3D fibrin-based scaffolds as a method of delivering neuronal cells derived from iPSCs -an important step toward the development of iPSC-based tissue engineering strategies for spinal cord injury repair.

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Section: 23supporting

confidence: 87%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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“…It is also difficult to obtain adult stem cells because of their limited quantities in the tissue. According to some previous literatures, they are considered to be composed of 0.01% to 0.001% of the total cell number (Hill et al, 2012;Rendl et al, 2005;Riekstina et al, 2009;Shim et al, 2013;Wegner and Stolt, 2005;Wu et al, 2010). We found that hDSPCs in small quantity gradually lose pluripotency and the ability to proliferate once they are grown over long-term culture.…”

Section: Introductionmentioning

confidence: 80%

“…On the contrary, a few intracellular specific markers are identified in dermal stem cells. SOX2, a SRY transcription factor, plays an essential role in maintaining stemness in embryonic stem cells and some adult stem cells such as the dermal papilla cells (Rendl et al, 2005;Wegner and Stolt, 2005). NANOG, another embryonic stem cell marker, is also expressed in adult mesenchymal stem cell populations derived from bone marrow, adipose tissue, and dermis (Hill et al, 2012;Riekstina et al, 2009;Szade et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Novel In Vitro Culture Condition Improves the Stemness of Human Dermal Stem/Progenitor Cells

Shim

Lee

Shin

2013

Molecules and Cells

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Cell therapy using adult stem cells has emerged as a potentially new approach for the treatment of various diseases. Therefore, it is an essential procedure to maintain the stemness of adult stem cells for clinical treatment. We previously reported that human dermal stem/progenitor cells (hDSPCs) can be enriched using collagen type IV. However, hDSPCs gradually lose their stem cell properties as in vitro passages continue. In the present study, we developed optimized in vitro culture condition to improve the stemness of these hDSPCs. To evaluate whether the stemness of hDSPCs is well sustained in various culture conditions, we measured the expression levels of SOX2, NANOG, and S100B, which are well-known representative dermal progenitor markers. We observed that hDSPCs grown in three-dimensional (3D) culture condition had higher expression levels of those markers compared with hDSPCs grown in two-dimensional (2D) culture condition. Under the 3D culture condition, we further demonstrated that a high glucose (4.5 g/L) concentration enhanced the expression levels of the dermal progenitor markers, whereas O 2 concentration did not affect. We also found that skin-derived precursor (SKP) culture medium was the most effective, among various culture media, in increasing the dermal progenitor marker expression. We finally demonstrated that this optimized culture condition enhanced the expression level of human telomerase reverse transcriptase (hTERT), the proliferation, and the multipotency of hDSPCs, an important characteristic of stem cells. Taken together, these results suggested that this novel in vitro culture condition improves the stemness of hDSPCs.

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“…[38][39][40] The SOX genes are divided into subfamilies primarily based on the amino-acid sequence homology of the HMG domain. 41 SOX10 is thought to have an essential role in differentiation of neural crest into Schwann cells, astrocytes and oligodendrocytes.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma

et al. 2014

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Synovial sarcoma and malignant peripheral nerve sheath tumor pose a significant diagnostic challenge given similar histomorphology. The distinction is further complicated by similar immunophenotype and especially by occasional synovial sarcomas that present as intraneural tumors. Although the presence of a t(X;18) rearrangement or expression of TLE1 can help confirm the diagnosis of synovial sarcoma, negative results for these tests are not diagnostic of malignant peripheral nerve sheath tumor. The SOX10 transcription factor, a putative marker of neural crest differentiation, may have diagnostic utility in this differential, but immunohistochemical data are limited. The goal of the present study was to determine the diagnostic utility of SOX10 to discriminate between synovial sarcoma and malignant peripheral nerve sheath tumor. Forty-eight cases of malignant peripheral nerve sheath tumor, all from patients with documented neurofibromatosis, and 97 cases of genetically confirmed synovial sarcoma, including 4 intraneural synovial sarcomas, were immunohistochemically stained for SOX10. The stain was scored for intensity and fraction of cells staining. Thirty-two of 48 malignant peripheral nerve sheath tumors (67%) were SOX10-positive. The majority of malignant peripheral nerve sheath tumors showed Z2 þ staining, but staining did not correlate with grade. By contrast, only 7/97 (7%) synovial sarcomas were SOX10-positive. Only three synovial sarcomas showed Z2 þ staining but, importantly, two of these were intraneural synovial sarcoma. Therefore, SOX10 is a specific (93%), albeit not very sensitive (67%), diagnostic marker to support a diagnosis of malignant peripheral nerve sheath tumor over synovial sarcoma. Furthermore, the stain needs to be interpreted with caution in intraneural tumors in order to avoid a potential diagnostic pitfall. It remains to be determined whether SOX10-positive cells in intraneural synovial sarcoma represent entrapped Schwann cells, synovial sarcoma cells or both.

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From stem cells to neurons and glia: a Soxist's view of neural development

Cited by 384 publications

References 68 publications

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Novel In Vitro Culture Condition Improves the Stemness of Human Dermal Stem/Progenitor Cells

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma

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