Age-maintained human neurons demonstrate a developmental loss of intrinsic neurite growth ability
Lear, B. P.; Thompson, E. A. N.; Rodriguez, K.; Arndt, Z. P.; Khullar, S.; Klosa, P. C.; Lu, R. J.; Morrow, C. S.; Risgaard, R.; Peterson, E. R.; Teefy, B. B.; Bhattacharyya, A.; Sousa, A. M. M.; Wang, D.; Benayoun, B. A.; Moore, D. L.
Show abstract
Injury to adult mammalian central nervous system (CNS) axons results in limited regeneration. Rodent studies have revealed a developmental switch in CNS axon regenerative ability, yet whether this is conserved in humans is unknown. Using human fibroblasts from 8 gestational-weeks to 72 years-old, we performed direct reprogramming to transdifferentiate fibroblasts into induced neurons (Fib-iNs), avoiding pluripotency which restores cells to an embryonic state. We found that early gestational Fib-iNs grew longer neurites than all other ages, mirroring the developmental switch in regenerative ability in rodents. RNA-sequencing and screening revealed ARID1A as a developmentally-regulated modifier of neurite growth in human neurons. These data suggest that age-specific epigenetic changes may drive the intrinsic loss of neurite growth ability in human CNS neurons during development. One-Sentence Summary: Directly-reprogrammed human neurons demonstrate a developmental decrease in neurite growth ability.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegeneration 95%
- Postmitotic accumulation of histone variant H3.3 in new cortical neurons establishes neuronal chromatin, transcriptome, and identity 95%
- Disruption of G3BP1 Granules Promotes Mammalian CNS and PNS Axon Regeneration 95%
Similar papers in this journal
- Neuronal Activation of the Gαq Protein EGL-30/GNAQ Late in Life Rejuvenates Cognition Across Species 96%
- The immune landscape of murine skeletal muscle regeneration and aging 95%
- Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation 94%
Similar papers in this journal
- Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to the human brain evolution 93%
- Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging 93%
- Autophagy counters inflammation-driven glycolytic impairment in aging hematopoietic stem cells 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.