Biology subjects

Chondronasiou, D.

Publications and source records attributed to Chondronasiou, D..

3 recordsLinked to original sources

bioRxiv2026

SENOMORPHIC EFFECT OF GENETIC AND CHEMICAL PARTIAL REPROGRAMMING

Partial reprogramming has emerged as a promising strategy to ameliorate aging phenotypes, yet its cellular targets and mechanisms remain poorly defined. Cellular senescence is a central hallmark of aging and a plausible mediator of reprogramming-induced rejuvenation. Here we show that genetic and chemical partial reprogramming act directly on senescent cells without restoring proliferative capacity. OSKM expression or a reduced two-compound regimen, tranylcypromine and RepSox (2c), attenuates senescence-associated secretory activity, restores mitochondrial homeostasis and apoptotic priming, and improves functional and inflammatory parameters in aged mice, establishing senomorphic, identity-preserving reprogramming as a potentially safer aging intervention.

cell biology↗

bioRxiv2022

Deciphering the roadmap of in vivo reprogramming towards pluripotency

Differentiated cells can be converted to pluripotent stem cells (iPSCs) upon ectopic expression of transcription factors OCT4, SOX2, KLF4 and MYC (OSKM) in a process known as reprogramming. Great efforts have been made to dissect intermediate states of in vitro reprogramming and how they are affected by culture conditions, while the roadmap of in vivo reprogramming remains unexplored. Here, we use single cell RNA sequencing to capture cells undergoing reprogramming in the adult pancreas. We identify markers along the trajectory from acinar identity to pluripotency, which allow in situ visualization of the intermediate states of reprogramming. Importantly, different tissues expressing OSKM, such as pancreas, stomach and colon, share markers of intermediate reprogramming, suggesting a conserved in vivo reprogramming path. Our in vivo roadmap defines landmarks along in vivo reprogramming that could be useful for applications in tissue regeneration and cellular rejuvenation based on intermediate reprogramming states.

developmental biology↗

bioRxiv2022

Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming

The expression of the pluripotency factors OCT4, SOX2, KLF4 and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, cycles of brief OSKM expression do not change cell identity but can reverse markers of aging in cells and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic and metabolomic changes towards a younger configuration in multiple tissues and in the serum.

cell biology↗