西亚试剂：Direct conversion of fibroblasts to functional neurons by d

发布时间：2025-07-09

Direct conversion of fibroblasts to functional neurons by defined factors

Thomas Vierbuchen1,2, Austin Ostermeier1,2, Zhiping P. Pang3, Yuko Kokubu1, Thomas C. Südhof3,4 & Marius Wernig1,2

1 Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology,
epartment of Molecular and Cellular Physiology,
2 Howard Hughes Medical Institute, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, California 94304, USA
3 Correspondence to: Marius Wernig1,2 Correspondence and requests for materials should be addressed to M.W.

Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.

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