Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Mexico City, Mexico.
Cell Transplant. 2021 Jan-Dec;30:963689720978219. doi: 10.1177/0963689720978219.
Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of and was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins βIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.
人类皮肤的表皮层含有角质形成细胞。这些细胞与中枢神经系统 (CNS) 具有共同的外胚层起源。最近的研究表明,终末分化的体细胞在异位表达转录因子后可以采用多能状态,或者可以直接将其表型转化为神经元。在本文中,我们测试了这样一个假设,即在神经培养基中悬浮培养人角质形成细胞后,它们可以采用神经命运。最初,角质形成细胞表达角蛋白和波形蛋白。在神经诱导后,观察到 和 转录上调,同时免疫染色检测到 NESTIN 显著增加。然而, 分化并未产生神经元或星形胶质细胞标记物的表达。我们通过超声引导注射将对照和神经诱导的角质形成细胞移植到大鼠发育中的中枢神经系统中,测试了它们的分化潜能。为此,用含有绿色荧光蛋白编码序列的慢病毒转染角质形成细胞。采用细胞分选选择高荧光细胞。出乎意料的是,在将这些细胞移植到脑室 4 天后,对照和神经诱导的细胞都表达了绿色荧光蛋白,以及神经元蛋白 βIII-微管蛋白和微管相关蛋白 2。这些结果支持了这样一种观点,即 环境提供了适当的信号来评估角质形成细胞或其他非神经细胞群体的神经元分化潜力。