Biology subjects

Puttonen, H.

Publications and source records attributed to Puttonen, H..

2 recordsLinked to original sources

bioRxiv2025

Multi-modal choroid plexus pathology in aging and Alzheimer's disease

Brain barriers, cerebrospinal fluid (CSF) dynamics, and peripheral factors are implicated as significant contributors to Alzheimers disease (AD). The choroid plexus (ChP) is a blood-brain interface that produces CSF and forms the blood-CSF barrier. However, how ChP pathology develops across the lifespan and contributes to AD has not been systematically characterized. Here, we report a multi-modal ChP atlas integrating single-nucleus transcriptomics from 49 individuals, AI-assisted quantitative histopathology across >500 postmortem samples age 16 to 105, spatial transcriptomics, and functional studies in 5xFAD mice. We identify fibrosis, calcification, and macrophage abnormalities as hallmarks of ChP aging, with AD pathology conferring additional effects, including expansion of a pro-inflammatory fibroblast-macrophage signaling niche. In 5xFAD mice, macrophage dysfunction is associated with impaired epithelial barrier maintenance and repair. Together, these data provide a foundational resource for understanding ChP dysfunction in aging and AD and propose the macrophage-fibroblast-epithelial barrier axis as a driver of ChP pathology.

neuroscience↗

bioRxiv2023

CRISPR/Cas9 DNA synthesis disruption as a tool to control cell proliferation in vitro and in vivo

Engineered cells hold great promise for regenerative medicine and gene therapy. However, living cell products entail a fundamental biological risk of unwanted growth. Here, we describe a novel metabolic safety system to control cell proliferation without added genetic elements. We inactivated a key enzyme for nucleotide metabolism, TYMS, in several cell lines, thus obtaining cells that proliferate only when supplemented with exogenous thymidine but fail to replicate in its absence. Under supplementation, TYMS-/- pluripotent stem cells proliferate normally, produce teratomas and differentiate into potentially therapeutic cell types such as pancreatic beta cells. After differentiation, the postmitotic cells do not require thymidine to function, as seen by prolonged in vivo production of human insulin in implanted mice. Hence, this method allows robust cell culture and manufacture while mitigating the risk of uncontrolled growth of transplanted cells. One Sentence Summary: Genetic disruption of DNA synthesis prevents unwanted proliferation in cell therapies without affecting cell function.

bioengineering↗