Biology subjects

Chiche, A.

Publications and source records attributed to Chiche, A..

5 recordsLinked to original sources

bioRxiv2025

In vivo risk assessment of yellow fever virus transmission through breastfeeding, and mechanistic insights

Yellow fever virus (YFV), a mosquito-borne flavivirus, remains a significant public health threat, especially in areas with low vaccine coverage. Since 2010, yellowfevervaccination is not recommended for breastfeeding women due to reported cases of vaccine strain transmission through breast milk, leading to neonatal meningoencephalitis. However, the efficiency of YFV vaccine strain transmission via breastfeeding remains unknown, and wild-type strains transmission may be suspected based on viral RNA detection in breast milk. Direct evidence of breastfeeding-related transmission in humans is challenging to obtain given the confounding presence of vector-borne transmission, making animal models crucial for evaluating this risk. In this study, the A129 mouse model was used to investigate YFV transmission via breastfeeding for both wild-type and vaccine strains. Results show that both strains can spread to mammary glands, leading to viral detection in breast milk as free viral particles and cell-associated virus, with similar viral loads for all strains. Mammary stromal and immune cells are primary targets of YFV in vivo, while mammary epithelial cells also support infection, suggesting two possible mechanisms of mammary epithelial crossing. Neonates are found to be susceptible to oral infection, with higher infection rates for the wild-type strain but evidence of neuroinvasion for both strains. Both strains can infect and cross an in vitro human intestinal barrier model, indicating this epithelium as a potential viral entry site for neonates. Finally, this study confirms the existence of YFV transmission through breastfeeding in an animal model, highlighting the need to consider it among transmission risks.

microbiology↗

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↗

bioRxiv2021

Amphiregulin mediates non-cell-autonomous effect of senescence on reprogramming

Cellular senescence is an irreversible growth arrest with a highly dynamic secretome, termed the senescence-associated secretory phenotype (SASP). Senescence has been implicated in somatic reprogramming to pluripotency. The cell-intrinsic proliferation arrest is a barrier for reprogramming, whereas the SASP facilitates the cell fate conversion in nonsenescent cells. However, the mechanisms by which reprogramming-induced senescence regulates cell plasticity are not well understood. Here, we have further investigated how the heterogeneity of paracrine senescence impacts reprogramming. We show that senescence promotes in vitro reprogramming in a stress-dependent manner. We identified a catalog of SASP factors and pathways potentially involved in the cell fate conversion using an unbiased proteomic analysis. Amphiregulin (AREG), a growth factor frequently secreted by the senescent cells, promotes in vitro reprogramming by accelerating proliferation and MET via the EGFR signaling pathway. Of note, AREG treatment diminished the negative effect of donor age on reprogramming. Finally, AREG enhances in vivo reprogramming in the skeletal muscle. Hence, senescence could facilitate cellular plasticity via various SASP factors to promote reprogramming and tissue repair.

cell biology↗

bioRxiv2019

Primary mammary organoid model of lactation and involution

Mammary gland development occurs mainly after birth and is composed of three successive stages: puberty, pregnancy and lactation, and involution. These developmental stages are associated with major tissue remodeling, including extensive changes in mammary epithelium as well as surrounding stroma. Three-dimensional (3D) mammary organoid culture has become an important tool in mammary gland biology and enabled invaluable discoveries on pubertal mammary branching morphogenesis and breast cancer. However, a suitable 3D organoid model recapitulating key aspects of lactation and involution has been missing. Here, we describe a robust and straightforward mouse mammary organoid system modeling lactation and involution-like process, which can be applied to study mechanisms of physiological mammary gland lactation and involution as well as pregnancy-associated breast cancer.

cell biology↗