BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons
BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons
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DOI：
10.3390/ijms21144947
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发表时间：
2020-07
影响因子：
5.6
通讯作者：
T. Yoshizumi;Atsuhiko Kubo;Hidetoshi Murata;M. Shinonaga;H. Kanno
中科院分区：
文献类型：
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作者：
T. Yoshizumi;Atsuhiko Kubo;Hidetoshi Murata;M. Shinonaga;H. Kanno
细胞因子信号传导抑制因子6 （SOCS6）中的BC-box基序促进包括表皮干细胞在内的体细胞干细胞的神经元分化。SOCS6蛋白属于SOCS蛋白群，抑制细胞因子信号传导。本研究表明，通过在细胞内传递由SOCS6蛋白BC-box基序编码的氨基酸序列组成的肽，表皮干细胞被诱导分化为GABAnergic神经元。SOCS6中的BC-box基序（SLQYLCRFVI）与长链蛋白BC的结合位点相对应。SOCS6蛋白BC-box基序介导的GABAnergic分化是由JAK2泛素化和JAK2- stat3通路的抑制引起的。此外，将表皮干细胞生成的gabanable神经元样细胞移植到啮齿动物脑缺血模型中。然后，我们证明这些移植细胞是GAD阳性的，移植细胞后的缺血性模型啮齿动物的认知功能得到改善。本研究不仅有助于阐明gaban能神经元分化的机制，而且有助于利用gaban能神经元进行神经再生医学研究。
The BC-box motif in suppressor of cytokine signaling 6 (SOCS6) promotes the neuronal differentiation of somatic stem cells, including epidermal stem cells. SOCS6 protein belongs to the group of SOCS proteins and inhibits cytokine signaling. Here we showed that epidermal stem cells were induced to differentiate into GABAnergic neurons by the intracellular delivery of a peptide composed of the amino-acid sequences encoded by the BC-box motif in SOCS6 protein. The BC-box motif (SLQYLCRFVI) in SOCS6 corresponded to the binding site of elongin BC. GABAnergic differentiation mediated by the BC-box motif in SOCS6 protein was caused by ubiquitination of JAK2 and inhibition of the JAK2-STAT3 pathway. Furthermore, GABAnergic neuron-like cells generated from epidermal stem cells were transplanted into the brain of a rodent ischemic model. Then, we demonstrated that these transplanted cells were GAD positive and that the cognitive function of the ischemic model rodents with the transplanted cells was improved. This study could contribute to not only elucidating the mechanism of GABAnergic neuronal differentiation but also to neuronal regenerative medicine utilizing GABAnergic neurons.