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keyuxi.bsky.social

@keyuxi.bsky.social
5 followers 6 following 13 posts

Bioengineering PhD @ Stanford | Greenleaf × Schnitzer labs | Chromatin, memory & single-cell genomics 🧠🧬

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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
A heartfelt thank you to William Greenleaf 🧬 and Mark Schnitzer 🧠 for guiding me through this adventure between genomics and neuroscience. What began as a grad student’s wild fuzzy idea became possible only through your trust, generous support, and countless conversations along the way. 13/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
Storing information as chromatin-encoded metaplastic rules that are engaged only during subsequent memory recall may be more energetically efficient than through ongoing maintenance of memory-related gene expression and protein expression. 12/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
One possible functional consequence of chromatin metaplasticity: to reduce interference between different memories by dampening the engagement of engram neurons to incoming information promoting new memory storage. 11/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
We call this chromatin metaplasticity: experience-dependent chromatin remodeling that changes a neuron’s capacity for future activity-dependent plasticity. Memory may preserve not only information about the past, but rules for how to change next. The future tense of memory. 10/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
These stimulus-to-chromatin pathways underlying memory also seem to be evolutionarily conserved and not neuron-specific, shared across distant systems, from unicellular organisms and neuron-less sponges to cancer cells. 9/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
These cells carry a latent, history-dependent state that changes how they respond to future cues, a writable state, stable against fluctuations. Lots of developmental programs being used. Now where have I seen that before… 🤔 (Hello developmental biologists!) 8/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
Back to chromatin. Engram-specific chromatin changes matured over weeks, weak at 7 d but prominent at 28 d, even without recall. 🧍🏻‍♀️ At 7 d, chromatin retained AP-1 signatures of recent activity. By 28 d, it shifted toward developmental and stable cell-state TF motifs. 7/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
We thought genes encoded effectors. Then Jacob–Monod (1961) showed they could encode regulators controlling other genes. This genomically encoded conditionality enables computation. Activity-dependent transcription is inducible transcription in neurons and is no different. 6/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
This was not simply stronger or weaker activity-dependent transcription. Engram neurons selectively rerouted recall responses, preferentially recruiting regulatory machinery: chromatin regulation, RNA processing, protein turnover etc. Not just genes directly making synapses stronger or weaker. 5/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
Without memory recall, engram and same-type non-engram excitatory neurons differed only modestly in RNA🧍🏻‍♀️ After recall, their transcriptional responses diverged broadly: Engram identity was revealed less by standing expression than by how neurons responded to recall 🏃🏻‍♀ 4/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
We found that: 1) engram neurons acquire memory-associated chromatin information a month after memory encoding; and that 2) chromatin information seems to reshape transcriptional responses at memory recall. A metaplasticity rule. 3/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
To answer this question, we combined activity-dependent genetic tagging + fear memory + single-nucleus multiome sequencing up to 4 weeks after memory encoding 🧠🧬 Why the prefrontal cortex? Its crucial role in long term memory: weeks to months in rodents, and years in humans. 2/13
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keyuxi.bsky.social @keyuxi.bsky.social · 11/08/2026
Chromatin has long been proposed to "store" memory related information; but what kind of information, contents or rules does it hold? Check out our new preprint: www.biorxiv.org/content/10.6... 1/13
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