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10/ ImN also showed decreased (in silico) intercellular communication in AD brains. In resilient individuals, they maintained crosstalk with other cells critical for anti-inflammatory and neuroprotective signaling. 🤝

9/ 🛡️ Resilient individuals—cognitively intact despite AD pathology—harbored ImN enriched for anti-inflammatory, anti-amyloidogenic, and neuroprotective transcriptional programs. These cells may actively buffer against AD progression. 💡

8/ We took extra steps to validate our findings using RNAScope in adult and fetal human brain & human iPSC-derived 3D cultures. Key marker combinations could detect ImN, and increased with hippocampal neuronal differentiation, indicating a role in human hippocampal neurogenesis. 🔬

7/ Yet, are these cells born in adulthood, passively waiting to mature when they ‘grow up’ or lingering remnants of embryonic neurogenesis? Maybe neither: ImN showed “youthful” transcriptional traits vs mature neurons, suggesting they may actively support hippocampal homeostasis.

6/ So, what did we find? Our quality control pipeline revealed the presence of immature neurons in adult GC! 🥳Enriched for immature markers, these populations were validated by trajectory inference and integration with the fetal neurogenic dataset.

5/ Back to the adult cohort: To screen for ImN signatures in adult GC and avoid false positives & negatives, we had to apply a rigorous pipeline: Ambient RNA removal, astrocyte and GC subsetting, empty droplet artifact filtering, unspliced RNA re-clustering. 🧹

4/ But what’s a good positive control for something that has not yet been thoroughly characterized? 🤔 We used fetal hippocampal tissue as a reference. In the fetal dentate gyrus, we observed clear neurogenic trajectories: neural stem cells → progenitors → ImN.

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3/ We had to enrich: We developed a new isolation protocol for sampling the dentate gyrus (granular cell layer & subgranular zone). This boosted granule cell (GC) detection to 54% (vs. 7–23% in prior studies) and enabled deep profiling of rare ImN signatures using snRNA-seq. 🎯

2/ What’s the deal with adult human ImN? These rare cells are known for being harder to find than a needle in a haystack. We profiled 110,527 high-quality nuclei from the hippocampus of 24 (healthy, moderate & severe AD, and dementia-resilient) donors using snRNA-seq.