BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons
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 di...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/4947 |
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| author | Tetsuya Yoshizumi Atsuhiko Kubo Hidetoshi Murata Masamichi Shinonaga Hiroshi Kanno |
| author_facet | Tetsuya Yoshizumi Atsuhiko Kubo Hidetoshi Murata Masamichi Shinonaga Hiroshi Kanno |
| author_sort | Tetsuya Yoshizumi |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:31:02Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e3c8c0818c344593a724efec3eee2fe12023-11-20T06:40:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114494710.3390/ijms21144947BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic NeuronsTetsuya Yoshizumi0Atsuhiko Kubo1Hidetoshi Murata2Masamichi Shinonaga3Hiroshi Kanno4Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, JapanNerve Care Clinic, Yokosuka 238-0012, JapanDepartment of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDepartment of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, JapanDepartment of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, JapanThe 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.https://www.mdpi.com/1422-0067/21/14/4947SOCS6 peptideepidermal stem cellsGABAnergic neuronneuronal differentiation |
| spellingShingle | Tetsuya Yoshizumi Atsuhiko Kubo Hidetoshi Murata Masamichi Shinonaga Hiroshi Kanno BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons International Journal of Molecular Sciences SOCS6 peptide epidermal stem cells GABAnergic neuron neuronal differentiation |
| title | BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons |
| title_full | BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons |
| title_fullStr | BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons |
| title_full_unstemmed | BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons |
| title_short | BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons |
| title_sort | bc box motif in socs6 induces differentiation of epidermal stem cells into gabanergic neurons |
| topic | SOCS6 peptide epidermal stem cells GABAnergic neuron neuronal differentiation |
| url | https://www.mdpi.com/1422-0067/21/14/4947 |
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