Highly efficient direct conversion of human monocytes into neuronal cells using a small molecule combination

Abstract

Investigation, I.N., and A.K.; Writing -Original Draft, I.N.; Writing -Review & Editing, I.N., M.K., A.K., M.H., and O.O.; Resources, M.K., and O.O.; Supervision, O.O. 2 SummaryPrevious studies reported that human fibroblasts and astrocytes were successfully converted into neuronal cells by small molecules without introducing ectopic transgenes.Induced neuronal cells-reprogrammed directly from dermal fibroblasts or brain astrocytes-were obtained from some donors; however, the clinical applications of this approach would be limited because it requires an invasive biopsy to harvest enough cells for derivation. Here, we report that adult human peripheral blood monocytes may be directly converted into neuron-like cells using only a combination of small molecules without transgene integration. This method enables neuronal cell generation from TUJ1-positive cells after 3 days of induction (at over 80% conversion efficacy). These cells presented neuronal morphologies and markers, suggesting that terminally differentiated human cells may be efficiently transdifferentiated into a distantly related lineage. Overall, our study provides a strategy to develop neuronal cells directly from human adult peripheral blood monocytes using a generate transgene-free, chemical-only approach.