Lifespan single-nucleus atlas of human dorsolateral prefrontal cortex
An abstract describes a single-nucleus transcriptomic atlas across the human lifespan, reporting non-linear, cell-type-specific transcriptional trajectories in the dorsolateral prefrontal cortex: remodelling in development, relative stability in midlife and selective molecular reactivation in late adulthood. [1]
Automatic summary · not editorially reviewed
The key findings
Most existing studies covered restricted age ranges or disease-affected brains, limiting separation of normative trajectories from pathological processes. [1]
The atlas reports non-linear, cell-type-specific transcriptional trajectories with remodelling in development, relative stability in midlife and selective reactivation in late adulthood. [1]
The authors present the findings as a framework for interpreting age-related cognitive decline and disease risk, not as causal or clinical evidence. [1]
The source at a glance
- Study type / format
- Single-nucleus transcriptomic atlas study (abstract).
- Population / context
- Human dorsolateral prefrontal cortex across the lifespan, as described in the abstract.
- Summary based on
- Study abstract
- Original publication
- September 23, 2026
Why a lifespan prefrontal cortex reference was lacking
The abstract states that the human brain changes profoundly from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease. The dorsolateral prefrontal cortex supports higher cognitive functions and is described as particularly sensitive to age-related decline, yet its cellular and molecular programs across the lifespan remained poorly defined. Most existing studies covered restricted age ranges or disease-affected brains, which the authors say limited the ability to separate normative developmental and ageing trajectories from pathological processes.
Supporting source [1]
Non-linear cell-type-specific trajectories in the atlas
Using a single-nucleus transcriptomic atlas spanning the human lifespan, the authors report that the dorsolateral prefrontal cortex shows non-linear, cell-type-specific transcriptional trajectories. These are characterized by dynamic remodelling during development, relative stability in midlife and selective molecular reactivation in late adulthood. They identify distinct neuronal and glial programs, including early-life neuronal resilience pathways and late-life glial programs associated with immune activation, stress responses and circadian reorganization. The programs are described as anatomically organized across cortical layers and grey-white matter domains.
Supporting source [1]
Framework for resilience to vulnerability, not a clinical test
The authors present these findings as a framework for understanding how cellular programs transition from resilience to vulnerability in the human cortex and as a foundation for interpreting age-related cognitive decline and disease risk. The abstract does not report sample sizes, age ranges, follow-up or how the atlas was validated, and it describes no intervention or clinical outcome. The described associations between transcriptional programs and ageing or disease risk are not shown to be causal, and the abstract does not establish any diagnostic or therapeutic use.
Supporting source [1]
How to interpret this
This is based on the abstract only; the full text was not reviewed. The abstract reports no sample size, age range, follow-up, validation or clinical outcomes, and the described associations are not causal.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Yang H, Clarence T, Scott MR, Wang X, N M P, Pjanic M, Venkatesh S, Hong A, Casey C, Murphy SR, Shao Z, Alvia M, Argyriou S, Yu AK, PsychAD Consortium, Tsankova NM, Auluck PK, Marenco S, Haroutunian V, Voloudakis G, Bendl J, McClung CA, Lee D, Fullard JF, Hoffman GE, Girdhar K, Roussos P. · europepmc.org · September 23, 2026