bims-caglex 2026-03-22 papers

Neuron. 2026 Mar 18. pii: S0896-6273(26)00134-0. [Epub ahead of print]114(6): 975-977

Rescuing specific memories by rejuvenating engram cells.

Partial cellular reprogramming can modulate aging-associated decline across multiple tissues. However, whether targeting memory-encoding ensembles within specific brain regions is sufficient to restore cognitive function has remained unknown. In this issue of Neuron, Berdugo-Vega et al. show that engram rejuvenation rescues memory deficits and restores epigenetic-transcriptional features and intrinsic excitability.

DOI: https://doi.org/10.1016/j.neuron.2026.02.029

Stem Cell Res Ther. 2026 Mar 20.

Rejuvenation of mesenchymal stromal cells via partial reprogramming enables scalable generation of transcriptionally diverse MSC libraries.

Haochen Tu, Aoi Hosaka, Genki Hichiwa, Yayan Wang, Kanako Kazuki, Toshiaki Tabata, Mitsuhiko Osaki, Yuji Nakayama, Iori Kanazawa, Kazuhisa Honma, Makoto T Kimura, Xu Gao, Norichika Ogata, Satoshi Abe, Mitsuo Oshimura, Yasuhiro Kazuki.

BACKGROUND: Mesenchymal stromal cells (MSCs) are widely used in regenerative medicine, but their clinical utility is limited by replicative senescence. Strategies that reverse aging while maintaining MSC identity are urgently needed.
METHODS: We developed a non-integrating, temperature-sensitive Sendai virus (SeV)-mediated rejuvenation protocol transiently expressing hTERT, BMI1, and SV40T in human MSCs. Following SeV removal, we evaluated proliferation, telomere length, karyotype stability, transcriptomic reset, producing heterogeneity, and differentiation potential.
RESULTS: Rejuvenated MSCs (rej-MSCs) demonstrated extended proliferation beyond 100 days, telomere elongation, and normal karyotypes after SeV clearance. Transcriptomic profiling showed a reset of senescence-associated programs while retaining mesenchymal identity. Functional analyses revealed clone-specific heterogeneity, including HGF-driven angiogenic activity. Multilineage differentiation capacity was preserved across rej-MSCs.
CONCLUSIONS: This transient, non-integrating rejuvenation strategy establishes an operational definition of rej-MSCs and provides a transcriptionally diverse and scalable platform for MSC manufacturing and precision therapy design.

Keywords: Mesenchymal stromal cells; Partial reprogramming; Regenerative medicine; Rejuvenation; Sendai virus

DOI: https://doi.org/10.1186/s13287-026-04977-8

Proc Natl Acad Sci U S A. 2026 Mar 24. 123(12): e2519117123

Phosphorylation and DNA damage resolution coordinate SOX2-mediated reprogramming in vivo.

Xiaoling Zhong, Yuhua Zou, Chun-Li Zhang.

The stem cell factor SOX2 can reprogram resident glial cells into neurons in the adult mammalian central nervous system, but the molecular mechanisms underlying this process remain poorly understood. Here, we show that both SOX2 phosphorylation and the PRKDC-dependent nonhomologous end joining (NHEJ) pathway are essential for SOX2-mediated in vivo glia-to-neuron reprogramming. A phospho-mimetic SOX2 mutant significantly enhances reprogramming output without altering neuronal fate. Conversely, loss of PRKDC or knockdown of core NHEJ components KU80 and LIG4 abolishes reprogramming. Notably, p53 knockdown restores reprogramming in PRKDC-deficient mice, likely by overcoming DNA damage-induced cell-cycle arrest. These findings demonstrate that SOX2-driven glial reprogramming requires both precise posttranslational regulation and effective DNA damage repair and suggest that targeting these pathways could enhance regenerative strategies in the CNS.

Keywords: NHEJ; PRKDC; SOX2; adult neurogenesis; glia-to-neuron reprogramming

DOI: https://doi.org/10.1073/pnas.2519117123