Malfunctioning CD106-positive, Short-term Hematopoietic Stem Cells Trigger Diabetic Neuropathy in Mice by Cell Fusion

Overview

Journal Commun Biol

Specialty Biology

Date 2021 May 15

PMID 33990693

Citations 6

Authors

Miwako Katagi

Tomoya Terashima

Natsuko Ohashi

Yuki Nakae

Akane Yamada

Takahiko Nakagawa

Itsuko Miyazawa

Hiroshi Maegawa

Junko Okano

Yoshihisa Suzuki

Kazunori Fujino

Yutaka Eguchi

Hideto Kojima

Affiliations

Soon will be listed here.

Abstract

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.

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