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Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion
Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121918/ https://www.ncbi.nlm.nih.gov/pubmed/33990693 http://dx.doi.org/10.1038/s42003-021-02082-5 |
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author | Katagi, Miwako Terashima, Tomoya Ohashi, Natsuko Nakae, Yuki Yamada, Akane Nakagawa, Takahiko Miyazawa, Itsuko Maegawa, Hiroshi Okano, Junko Suzuki, Yoshihisa Fujino, Kazunori Eguchi, Yutaka Kojima, Hideto |
author_facet | Katagi, Miwako Terashima, Tomoya Ohashi, Natsuko Nakae, Yuki Yamada, Akane Nakagawa, Takahiko Miyazawa, Itsuko Maegawa, Hiroshi Okano, Junko Suzuki, Yoshihisa Fujino, Kazunori Eguchi, Yutaka Kojima, Hideto |
author_sort | Katagi, Miwako |
collection | PubMed |
description | Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant fraction of short-term hematopoietic stem cells (ST-HSCs) that contribute to the development of diabetic neuropathy in mice. The important role for these cells is supported by the fact that transplantation of either whole HSCs or CD106-positive ST-HSCs from diabetic mice to non-diabetic mice produces diabetic neuronal dysfunction in the recipient mice via cell fusion. Furthermore, we show that transient episodic hyperglycemia produced by glucose injections leads to abnormal fusion of pathological ST-HSCs with residential neurons, reproducing neuropathy in nondiabetic mice. In conclusion, we have identified hyperglycemia-induced aberrant CD106-positive ST-HSCs underlie the development of diabetic neuropathy. Aberrant CD106-positive ST-HSCs constitute a novel therapeutic target for the treatment of diabetic neuropathy. |
format | Online Article Text |
id | pubmed-8121918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81219182021-05-17 Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion Katagi, Miwako Terashima, Tomoya Ohashi, Natsuko Nakae, Yuki Yamada, Akane Nakagawa, Takahiko Miyazawa, Itsuko Maegawa, Hiroshi Okano, Junko Suzuki, Yoshihisa Fujino, Kazunori Eguchi, Yutaka Kojima, Hideto Commun Biol Article Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant fraction of short-term hematopoietic stem cells (ST-HSCs) that contribute to the development of diabetic neuropathy in mice. The important role for these cells is supported by the fact that transplantation of either whole HSCs or CD106-positive ST-HSCs from diabetic mice to non-diabetic mice produces diabetic neuronal dysfunction in the recipient mice via cell fusion. Furthermore, we show that transient episodic hyperglycemia produced by glucose injections leads to abnormal fusion of pathological ST-HSCs with residential neurons, reproducing neuropathy in nondiabetic mice. In conclusion, we have identified hyperglycemia-induced aberrant CD106-positive ST-HSCs underlie the development of diabetic neuropathy. Aberrant CD106-positive ST-HSCs constitute a novel therapeutic target for the treatment of diabetic neuropathy. Nature Publishing Group UK 2021-05-14 /pmc/articles/PMC8121918/ /pubmed/33990693 http://dx.doi.org/10.1038/s42003-021-02082-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Katagi, Miwako Terashima, Tomoya Ohashi, Natsuko Nakae, Yuki Yamada, Akane Nakagawa, Takahiko Miyazawa, Itsuko Maegawa, Hiroshi Okano, Junko Suzuki, Yoshihisa Fujino, Kazunori Eguchi, Yutaka Kojima, Hideto Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion |
title | Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion |
title_full | Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion |
title_fullStr | Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion |
title_full_unstemmed | Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion |
title_short | Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion |
title_sort | malfunctioning cd106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121918/ https://www.ncbi.nlm.nih.gov/pubmed/33990693 http://dx.doi.org/10.1038/s42003-021-02082-5 |
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