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Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes. Proactive treatment options remain limited, largely due to a lack of sensitive and convenient diagnostics, especially early in disease progression or specifically for small fiber neuropathy (SFN), the dying back of distal small diameter nerves. Here, we report on the design, testing, and validation of a novel medical diagnostic device for the functional assessment of small fiber nerves: an electrically conductive needle array designed to record nerve activity signals in the skin and transdermal tissues, which we call the DEN (Detecting Early Neuropathy). DEN recordings were validated across a time course of high fat diet-induced DPN in mice. Based on preclinical mouse data, the device was then adapted to obtain recordings in human tissue. DEN recordings successfully recorded various types of neural activity. New functional diagnostic tools like DEN offer a promising outlook for patients needing an earlier and more sensitive diagnosis of SFN/DPN, which will allow for earlier and more effective treatment options such as implementation of glucose regulation strategies.

Telomerase reverse transcriptase (TERT) is expressed by quiescent adult stem cells (ASC) in numerous adult murine and human tissues, but has never been explored in the adult brain. Here, we demonstrate that TERT+ cells in the adult mouse brain represent a novel population of multipotent ASCs that are localized to numerous classical neuro/gliogenic niches (including the ventricular-subventricular zone, hypothalamus, and olfactory bulb), as well as more recently described regions of adult brain plasticity such as the meninges and choroid plexus. Using a direct-reporter mouse line, we found that TERT+ cells expressed known neural stem cell markers such as Nestin and Sox2, but not markers of committed stem/progenitor cells, nor markers of mature neuronal or glial cells. TERT+ ASCs rarely expressed the proliferation marker Ki67, andin vitroTERT+ cells lost TERT expression when activated by growth factors, together indicating a quiescent phenotype similar to what has been observed in other tissues. When cultured, TERT+ cells behaved like neural stem cells by forming neurospheres, which could proliferate and become more metabolically active once stimulated by growth factors. TERT+ cells were observed in numerous brain niches, particularly near the ventricles and cerebrospinal fluid barriers, but notably, TERT+ cells were never observed in the hippocampus. Lineage tracing of TERT+ cells in adult transgenic mice (mTERTrtTA::oTET-Cre::RosamTmG) revealed large-scale expansion of TERT+ progeny and differentiation to diverse cell types in multiple brain regions. For example, lineage-traced cells expressed markers of mature neurons, oligodendrocytes, astrocytes, ependymal cells, and choroid epithelial cells, thus demonstrating the striking multipotency of this stem cell population in basal tissue turnover of the adult brain. Together, these data demonstrate that TERT+ cells represent a novel population of multipotent stem cells that contribute to basal plasticity and regeneration in the adult mouse brain.Graphical Abstract