vittorio Profile picture
Mar 14, 2025 13 tweets 3 min read Read on X
holy shit

MIT researchers just turned skin cells directly into neurons without stem cell intermediate, 100-fold efficiency boost, and they actually worked when transplanted into mouse brains

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before, converting skin cells into neurons meant a messy detour through induced pluripotent stem cells (iPSCs). slow, inefficient (~1%), and cells often got stuck half-way, wasting weeks and resources.

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MIT's breakthrough bypasses the iPSC bottleneck entirely. they tweaked the conversion cocktail down to just 3 transcription factors (Ngn2, Isl1, Lhx3) plus two genes boosting proliferation, sending neuron yield to over 1000%. real neurons, real fast.

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how it works:

researchers engineered skin cells from mice using a single retrovirus to deliver these factors, ensuring precise expression levels in each cell. simpler method, fewer errors, massive efficiency.

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core innovation:

cells were pushed into hyperproliferation first, dramatically increasing their receptivity to the transcription factors. basically, MIT primed cells into a hyper-responsive state before flipping the neuron switch.

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why this speeds things up:

hyperproliferation boosts conversion success by 4x. cells aren’t just more numerous, they’re also more receptive. conversion is faster (just two weeks), yielding morphologically mature motor neurons ready to be used

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the most impressive data point is that the yield jumped from below 1% with old methods to 1100% with this new cocktail. over ten neurons per single original skin cell.

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neurons implanted into mouse brains survived and integrated, showing electrical activity and calcium signaling. these aren't lab curiosities, they're real, functional neurons.

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this removes the old belief that direct cell conversions were inevitably low-yield and practically unusable. MIT just made direct neuron conversion viable at scale.

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proliferation history fundamentally shapes cell fate decisions, redefining how we think about cell reprogramming. controlling proliferation + TF levels = massive leap in regenerative medicine.

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some could point to oncogenes (cancer risk) used to boost proliferation. but experiments confirm neurons quickly become non-proliferative and stable post-conversion and the oncogenic risks is minimal.

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this could have immediate applications in spinal cord injury, ALS, and motor neuron diseases, rapidly producing functional neurons for therapy and drug screening.
but also personalized BCI, biological processors and computing, neuroprosthetics, regenerative neurotech, etc

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