Tracing the stemness of porcine skin-derived progenitors (pSKP) back to specific marker gene expression.

Mingtao Zhao, S Clay Isom, Hui Lin, Yanhong Hao, Yong Zhang, Jianguo Zhao, Jeffrey J Whyte, Kyle B Dobbs, Randall S Prather
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引用次数: 40

Abstract

Multipotent skin-derived progenitors (SKP) can produce both neural and mesodermal progeny in vitro, sharing the characteristics of embryonic neural crest stem cells. However, the molecular basis for the property of multiple lineage potential and neural crest origin of SKPs is still elusive. Here we report the cooperative expression of pluripotency related genes (POU5F1, SOX2, NANOG, STAT3) and neural crest marker genes (p75NTR, TWIST1, PAX3, SNAI2, SOX9, SOX10) in GFP-transgenic porcine skin-derived progenitors (pSKP). The proportion of cells positive for POU5F1, nestin, fibronectin, and vimentin were 12.3%, 15.1%, 67.9% and 53.7%, showing the heterogeneity of pSKP spheres. Moreover, pSKP cells can generate both neural (neurons and glia) and mesodermal cell types (smooth muscle cells and adipocytes) in vitro, indicating the multiple lineage potency. Four transcription factors (POU5F1, SNAI2, SOX9, and PAX3) were identified that were sensitive to mitogen (FBS) and/or growth factors (EGF and bFGF). We infer that POU5F1, SNAI2, SOX9, and PAX3 may be the key players for maintaining the neural crest derived multipotency of SKP cells in vitro. This study has provided new insight into the molecular mechanism of stemness for somatic-derived stem cells at the level of transcriptional regulation.

猪皮肤源性祖细胞(pSKP)的干性溯源至特定的标记基因表达。
多能皮肤源性祖细胞(SKP)可以在体外产生神经和中胚层的后代,具有胚胎神经嵴干细胞的特征。然而,SKPs的多谱系电位特性和神经嵴起源的分子基础尚不清楚。本研究报道了多能性相关基因(POU5F1、SOX2、NANOG、STAT3)和神经嵴标记基因(p75NTR、TWIST1、PAX3、SNAI2、SOX9、SOX10)在转gfp的猪皮肤源性祖细胞(pSKP)中的协同表达。POU5F1、巢蛋白、纤维连接蛋白和vimentin阳性细胞比例分别为12.3%、15.1%、67.9%和53.7%,显示pSKP球的异质性。此外,pSKP细胞在体外可以生成神经细胞(神经元和胶质细胞)和中胚层细胞(平滑肌细胞和脂肪细胞),表明其具有多谱系能力。4个转录因子(POU5F1、SNAI2、SOX9和PAX3)对丝裂原(FBS)和/或生长因子(EGF和bFGF)敏感。我们推测,POU5F1、SNAI2、SOX9和PAX3可能是体外维持神经嵴源性SKP细胞多能性的关键因子。本研究在转录调控水平上对体细胞干细胞的干性分子机制提供了新的认识。
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