SENESCENT DERMAL PAPILLA CELLS INDUCE PARACRINE SENESCENCE ON HAIR FOLLICLE PRECURSORS, ALTERING THEIR COMMITMENT TO HAIR LINEAGE

MARTINEZ , NAHUEL; HAGELIN, KARIN; PROIETTI, CECILIA JAZMIN; BALAÑA, MARIA EUGENIA; CERUTI, JULIETA MARÍA

Buenos Aires

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIAS SAIC;SAFIS ; ALACF; 2024

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Hair follicle cyclic regeneration is induced when hair follicle stem cells (HFSC) are activated by dermal papilla cells (DPC). This process is significantly impacted by aging. We established an UVB-induced senescence model in human DPC spheroids and observed that senescent DPC have impaired their inductivity signaling. Considering reported effects of senescence in cell plasticity, we aimed to study the paracrine effect of senescent DPC on HFSC senescence, stemness and plasticity. HFSC cultured with conditioned medium from UVB treated DPC showed higher SA-β-galactosidase activity (13,89%) than HFSC cultured with non-treated DPC medium (3,85%) and non-conditioned medium (0,96%) indicating an increase in paracrine senescence. Proliferation of HFSC was compromised when cultured with both conditioned media, however, cells cultured with UVB-treated DPC medium restored their proliferation capability in later stages (62,85% vs 40,34%). The proliferation stop correlated with an augment in cell cycle inhibitors p21 and p19. On the other hand, metabolic activity increased in HFSC cultured with both conditioned media compared with non-treated HFSC. HFSC cultured with UVB-DPC medium showed an upregulation of senescence associated secretory phenotype (SASP) genes (IL-1α, IL-1β, IL-6, MMP-1, MMP3) and diminished expression of Lamin-B1 senescence marker. We also observed the downregulation of K19 and alterations in Nfgr and Nestin stemness genes expression. Our study demonstrates that UVB-induced senescent DPC have a paracrine effect on hair follicle keratinocytes, impacting hair follicle regeneration. We found that conditioned medium from UVB-treated DPC increased senescence markers in HFSC, such as SA-β-galactosidase activity and SASP expression, suggesting enhanced paracrine senescence signaling compared to non-treated DPC. Moreover, alterations in stemness gene expression let us infer changes in HFSC plasticity to diverse cell fates like skin or sebaceous gland lineages.