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Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion.

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.

SUBMITTER: Katagi M

PROVIDER: S-EPMC8121918 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundClimate change is increasing global average temperatures, as well as the frequency of extreme weather events. Both low and high ambient temperatures have been associated with elevated mortality; however, little is known about the cardiovascular impacts of hourly temperature.MethodsWe assessed the association between hourly ambient temperature and risk of myocardial infarction (MI) across adult residents of New York State (NYS). We identified cases across NYS hospitals from 2000 to 2015 in the New York Department of Health Statewide Planning and Research Cooperative System dataset, using ICD codes. Hourly ambient temperature was assessed at each patient's residential ZIP code, up to 48 hours prior to MI. We employed a time-stratified case-crossover study design matching case to control periods on hour of day, day of week, month and year.ResultsOf the 791,695 primary MI hospital admissions, 45% were female, the mean (standard deviation; SD) age was 70 (15) years, and 49% of cases occurred among New York City residents. The observed temperature range was -29 °C to 39 °C, with a mean of 10.8 °C (10.5 °C). Temperature in the 6 h preceding the MI was positively associated with risk of MI, across the range of observed temperatures, with null or nearly null associations for earlier hours. We estimated a cumulative percent increase in hourly myocardial infarction rate of 7.9% (95% confidence interval [CI]: 5.2%, 10.6%) for an 11 °C (median) to 27 °C (95th percentile) temperature increase for lag hours 0-5. Men, Medicare-ineligible individuals (age < 65), and those experiencing their first MI were most sensitive.ConclusionOur study provides evidence that increases in hourly ambient temperature can trigger myocardial infarction. Health-based definitions of extreme heat events may better capture the deleterious effects of heat by accounting for hourly temperature. Our findings can inform the design of more effective preparedness strategies for the increasingly frequent extreme heat events.

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Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion.

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