Stem cells repurpose proliferation to contain a breach in their niche barrier.

Adult stem cells are responsible for life-long tissue maintenance. They reside in and interact with specialized tissue microenvironments (niches). Using murine hair follicle as a model, we show that when junctional perturbations in the niche disrupt barrier function, adjacent stem cells dramatically change their transcriptome independent of bacterial invasion and become capable of directly signaling to and recruiting immune cells. Additionally, these stem cells elevate cell cycle transcripts which reduce their quiescence threshold, enabling them to selectively proliferate within this microenvironment of immune distress cues. However, rather than mobilizing to fuel new tissue regeneration, these ectopically proliferative stem cells remain within their niche to contain the breach. Together, our findings expose a potential communication relay system that operates from the niche to the stem cells to the immune system and back. The repurposing of proliferation by these stem cells patch the breached barrier, stoke the immune response and restore niche integrity.

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The Microbiome in Atopic Dermatitis

As an interface with the environment, the skin is a complex ecosystem, colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens such as S. aureus and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized, as microorganisms can modulate innate, as well as adaptive, immune responses. Host-commensal interactions also have an impact on the developing immune system in infants and subsequently the occurrence of diseases such as asthma and atopic dermatitis. Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with atopic dermatitis, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria such as S. aureus. Early clinical studies suggest that topical application of commensal organisms (e.g., S. hominis or R. mucosa) reduces atopic dermatitis severity and support an important role for commensals in decreasing S. aureus colonization in patients with atopic dermatitis. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders such as atopic dermatitis may result in novel therapeutic strategies.

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Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease.

Stem cells regenerate tissues in homeostasis and under stress. By taking cues from their microenvironment or “niche,” they smoothly transition between these states. Immune cells have surfaced as prominent members of stem cell niches across the body. Here, we draw parallels between different stem cell niches to explore the context-specific interactions that stem cells have with tissue-resident and recruited immune cells. We also highlight stem cells’ innate ability to sense and respond to stress and the enduring memory that forms from such encounters. This fascinating crosstalk holds great promise for novel therapies in inflammatory diseases and regenerative medicine.

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The healing power of painful memories

Naik, S. The healing power of painful memories. Science 359(6380): 1113 March 2018

Our body’s epithelia are barriers that interface with the terrestrial environment and routinely experience inflammation. Although a vast majority of these inflammatory reactions resolve, they imprint the tissue with a memory. Cells of the immune system are traditionally thought to be the bearers of this memory, allowing them to react faster to subsequent inflammatory pressures (1, 2). Yet, barrier tissues are composites of epithelial, mesenchymal, nervous, vascular, and immunological networks working in unison to sustain optimal function in health and disease. The question of whether tissue-resident cells, distinct from the immune system, are entrained in response to a perturbation remains to be addressed.

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Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.

Naik S*, Larsen SB*, Gomez N, Alaverdyan K, Sendoel A, Polak L, Kulukian A, Chai S and Fuchs E. Inflammatory memory sensitizes skin epithelial stem cells to tissue damage. *Equal author contribution. Corresponding author. Nature. 550(7677): 475-480 Oct 2017

Here we report that acute inflammation trains epithelial stem cells to respond faster to subsequent stressors. This work is the first to identify inflammatory memory in a non-immune cells and has significant implications for our understanding of inflammatory diseases and cancer.

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