Biology subjects

Chantrel, J.

Publications and source records attributed to Chantrel, J..

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↗

bioRxiv2024

Induction of Senescence During Postpartum Mammary Gland Involution supports tissue remodeling and promotes postpartum tumorigenesis

Cellular senescence is an evolutionarily conserved stress response1, yet its roles during physiological processes remain underexplored2,3. Senescent cells are known to promote tissue repair4,5 and suppress tumorigenesis6, but their accumulation contributes to various pathological and physiological processes, including cancer and ageing7-9. However, it is currently unknown whether physiological senescence can be co-opted by oncogenic events to promote tumorigenesis. Postpartum mammary gland involution is a major tissue remodelling event in adulthood10,11, resembling the wound healing process, and is closely linked to postpartum breast cancer (PPBC)12 providing a compelling context to investigate this question. Here, we show that senescence is induced in alveolar luminal cells during involution in a p16-dependent manner. Reducing senescent cells hinders tissue remodeling and delays involution, underscoring their physiological importance. However, using a PPBC mouse model where the oncogenic event coincides with involution, we demonstrate that eliminating involution-associated senescent cells markedly extended the cancer latency. Mechanistically, we reveal that senescent cells enhance tumor-initiating cell plasticity in a paracrine manner, promoting tumor invasion and metastasis. Collectively, our findings uncover a dual role of senescence in mediating postpartum tissue remodeling and promoting tumorigenesis, highlighting a scenario where physiological senescence is hijacked to drive cancer progression. This work underscores that senescence might be a unifying mechanism linking tissue repair to tumorigenesis.

cell biology↗

bioRxiv2023

Single-cell RNAseq reveals the pro-regenerative role of senescent FAPs in muscle regeneration

Muscle regeneration is associated with transient induction of cellular senescence. However, the role of senescence in muscle regeneration of young mice remains unclear. Using a mouse model deficient in both Cdkn1a and Cdkn2a, we find that a marked reduction in senescent cells correlates with delayed muscle regeneration. Single-cell RNA sequencing reveals a heterogeneous senescence program composing of multiple cell types. Notably, senescent fibro-adipogenic progenitors (FAPs) upregulate Mcl-1 to acquire apoptosis resistance. Moreover, removing senescent FAPs using a Mcl-1 inhibitor S63845 impairs muscle regeneration. Furthermore, we find that senescent FAPs promotes myogenic differentiation in a paracrine manner. Hence, these results highlight the beneficial role of senescent stromal cells in supporting muscle regeneration.

developmental biology↗