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Falcone, C.

Publications and source records attributed to Falcone, C..

2 recordsLinked to original sources

Transcription, structure, and organoids translate time across the lifespan of humans and great apes

How the neural structures supporting human cognition develop and arose in evolution is an enduring question of interest. Yet, we still lack appropriate procedures to align ages across primates, and this lacuna has hindered progress in understanding the evolution of biological programs. We generated a dataset of unprecedented size consisting of 573 time points from abrupt and gradual changes in behavior, anatomy, and transcription across human and 8 non-human primate species. We included time points from diverse human populations to capture within-species variation in the generation of cross-species age alignments. We also extracted corresponding ages from organoids. The identification of corresponding ages across the lifespan of 8 primate species, including apes (e.g., orangutans, gorillas) and monkeys (i.e., marmosets, macaques) reveal that some biological pathways are extended in humans compared with some non-human primates. Particularly, the human lifespan is unusually extended relative to studied nonhuman primates demonstrating that very old age is a phase of life in humans that does not map to other studied primate species. More generally, our work prompts a reevaluation in the choice of a model system to understand aging given very old age in humans is a period of life with a clear counterpart in great apes. Significance StatementWhat is special about the duration of human development and aging has been an enduring source of interest. A significant hurdle in identifying which biological programs are unusually extended in humans is the lack of standardized approaches with which to align ages across species. We harnessed temporal variation in behavior, transcription, and anatomy to align ages across the lifespan of primates. These data reveal which biological programs are conserved, and which are modified. Harnessing time points across scales of study guides the choice of model systems to understand disease progression, and can be used to enhance care of great apes, many of which are critically endangered.

neuroscience↗

Oligodendrocytes are a lifelong source of nuclear and ribosomal material for neurons in the mouse brain

Nuclear and ribosomal components define cell identity and function by regulating chromatin dynamics, gene expression, and protein turnover. Here we report that in the mouse central nervous system (CNS) under normal conditions, neurons accumulate nuclear and ribosomal material of oligodendrocyte (OL) origin. We show that neuronal accumulation of OL-derived nuclear and ribosomal material is brain area-specific, and in the cortex and hippocampal dentate gyrus gradually propagates during postnatal brain maturation. We further demonstrate that OL-to-neuron material transfer persists throughout adulthood and responds to neuroinflammation. We found that satellite OL of the gray matter form internuclear contacts with receiving neurons in the mouse brain. Similar close internuclear associations between satellite OL and neurons are present in the adult human cortex. Our findings provide the first evidence of wide-spread dynamic and selective OL-to-neuron nuclear and ribosomal material transfer in the mouse CNS and indicate that satellite OL serve as powerful mediators of neuronal function. Equivalent processes may occur in the human CNS and cause neurological disorders when dysregulated. One Sentence SummaryNeurons receive OL-derived nuclear and ribosomal material

neuroscience↗