Dynamic regulation of tissue fluidity controls skin repair during wound healing.

During wound healing, different pools of stem cells (SCs) contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for skin repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing and basal cell lineage ablation, we monitor SC fate and tissue dynamics during regeneration using confocal and intravital imaging. Analysis of basal cell rearrangements shows dynamic transitions from a solid-like homeostatic state to a fluid-like state allowing tissue remodeling during repair, as predicted by a minimal mathematical modeling of the spatiotemporal dynamics and fate behavior of basal cells. The basal cell layer progressively returns to a solid-like state with re-epithelialization. Bulk, single-cell RNA, and epigenetic profiling of SCs, together with functional experiments, uncover a common regenerative state regulated by the EGFR/AP1 axis activated during tissue fluidization that is essential for skin SC activation and tissue repair.

The extracellular matrix dictates regional competence for tumour initiation.

The skin epidermis is constantly renewed throughout life1,2. Disruption of the balance between renewal and differentiation can lead to uncontrolled growth and tumour initiation3. However, the ways in which oncogenic mutations affect the balance between renewal and differentiation and lead to clonal expansion, cell competition, tissue colonization and tumour development are unknown. Here, through multidisciplinary approaches that combine in vivo clonal analysis using intravital microscopy, single-cell analysis and functional analysis, we show how SmoM2-a constitutively active oncogenic mutant version of Smoothened (SMO) that induces the development of basal cell carcinoma-affects clonal competition and tumour initiation in real time. We found that expressing SmoM2 in the ear epidermis of mice induced clonal expansion together with tumour initiation and invasion. By contrast, expressing SmoM2 in the back-skin epidermis led to a clonal expansion that induced lateral cell competition without dermal invasion and tumour formation. Single-cell analysis showed that oncogene expression was associated with a cellular reprogramming of adult interfollicular cells into an embryonic hair follicle progenitor (EHFP) state in the ear but not in the back skin. Comparisons between the ear and the back skin revealed that the dermis has a very different composition in these two skin types, with increased stiffness and a denser collagen I network in the back skin. Decreasing the expression of collagen I in the back skin through treatment with collagenase, chronic UV exposure or natural ageing overcame the natural resistance of back-skin basal cells to undergoing EHFP reprogramming and tumour initiation after SmoM2 expression. Altogether, our study shows that the composition of the extracellular matrix regulates how susceptible different regions of the body are to tumour initiation and invasion.

HIV-Infected Mothers Who Decide to Breastfeed Their Infants Under Close Supervision in Belgium: About Two Cases.

Introduction: In most industrialized countries, human immunodeficiency virus (HIV) infection remains a formal contraindication to breastfeeding. However, for the past 9 years, the World Health Organization (WHO) has recommended, for developing countries, that mothers infected with HIV and treated by combined antiretroviral therapy (cART) should breastfeed their infants. HIV-infected women coming from developing countries and living in industrialized settings are increasingly expressing their natural desire to breastfeed. To avoid uncontrolled breastfeeding practices and reduce the risk of mother-to-child transmission of the virus, there is an urgent need to consider the wishes of these women. Discussion: We report two cases in which specific guidelines were implemented in order to support the mothers' choice to breastfeed in Belgium. As a result of different prophylactic measures including antiretrovirals in mothers and infants and close follow-up, none of the infants were infected. Conclusions: National or international recommendations for HIV-infected mothers who choose to breastfeed in industrialized countries remain unclear and discordant. There is an unmet need for experts to address this emerging issue and to develop an international consensus for the monitoring and prophylactic management of exposed-infants.