A study published in Nature demonstrates that human fibroblasts can be directly converted into functional neurons using a combination of three transcription factors: Brn2, Ascl1, and Myt11. This method allows for the rapid generation of induced neuronal (iN) cells from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors can convert fetal and postnatal human fibroblasts into iN cells that display typical neuronal morphologies and express multiple neuronal markers. These iN cells can generate action potentials and mature to receive synaptic contacts when co-cultured with primary mouse cortical neurons. The study also shows that the BAMN factors (Brn2, Ascl1, Myt11, and NeuroD1) can efficiently convert human fibroblasts into neurons, with the most mature neuronal morphologies observed when all four factors are used together. The iN cells exhibit robust synaptic responses and can form functional synapses when co-cultured with mouse cortical neurons. The study highlights the potential of these methods for generating patient-specific human neurons for in vitro disease modeling and regenerative medicine. The research also demonstrates that the iN cell state is stable even without continued transgene expression, as endogenous genes are rapidly induced and exhibit increasing expression levels over time. The study provides a detailed analysis of the membrane properties, synaptic responses, and gene expression profiles of the iN cells, showing that they can express functional neurotransmitter receptors and form functional synapses. The findings suggest that the direct conversion of human fibroblasts into neurons using defined transcription factors is a promising approach for generating neurons for research and therapeutic applications.A study published in Nature demonstrates that human fibroblasts can be directly converted into functional neurons using a combination of three transcription factors: Brn2, Ascl1, and Myt11. This method allows for the rapid generation of induced neuronal (iN) cells from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors can convert fetal and postnatal human fibroblasts into iN cells that display typical neuronal morphologies and express multiple neuronal markers. These iN cells can generate action potentials and mature to receive synaptic contacts when co-cultured with primary mouse cortical neurons. The study also shows that the BAMN factors (Brn2, Ascl1, Myt11, and NeuroD1) can efficiently convert human fibroblasts into neurons, with the most mature neuronal morphologies observed when all four factors are used together. The iN cells exhibit robust synaptic responses and can form functional synapses when co-cultured with mouse cortical neurons. The study highlights the potential of these methods for generating patient-specific human neurons for in vitro disease modeling and regenerative medicine. The research also demonstrates that the iN cell state is stable even without continued transgene expression, as endogenous genes are rapidly induced and exhibit increasing expression levels over time. The study provides a detailed analysis of the membrane properties, synaptic responses, and gene expression profiles of the iN cells, showing that they can express functional neurotransmitter receptors and form functional synapses. The findings suggest that the direct conversion of human fibroblasts into neurons using defined transcription factors is a promising approach for generating neurons for research and therapeutic applications.