Under pressure: Stem cell-niche interactions coordinate tissue adaptation to inflammation

Stem and progenitor cells (SCs) are emerging as key drivers of tissue adaptation to inflammation caused by microbes, injury, noxious agents, and other onslaughts. These pressures are most acutely experienced in epithelial tissues such as the skin and gut that interface with the external environment. Thus, here we review how epithelial SCs of the skin and intestine, along with their supportive niches, sense and respond to inflammation for the sake of preserving tissue integrity. We highlight inflammation-induced plasticity in SCs and their progeny and the lasting memory that forms thereafter. The burgeoning area of SC responses to inflammatory stressors may expand therapeutic perspectives in epithelial inflammatory conditions, wound repair, cancers, and aging.

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Deciphering the regulatory landscape of fetal and adult γδ T-cell development at single-cell resolution

Sagar et al. DOI: 10.15252/embj.2019104159

γδ T cells with distinct properties develop in the embryonic and adult thymus and have been identified as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases, and tissue homeostasis. Despite their potential value for immunotherapy, differentiation of γδ T cells in the thymus is incompletely understood. Here, we establish a high-resolution map of γδ T-cell differentiation from the fetal and adult thymus using single-cell RNA sequencing. We reveal novel sub-types of immature and mature γδ T cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult γδ T-cell differentiation. By performing a combined single-cell analysis of Sox13, Maf, and Rorc knockout mice, we demonstrate sequential activation of these factors during IL-17-producing γδ T-cell (γδT17) differentiation. These findings substantially expand our understanding of γδ T-cell ontogeny in fetal and adult life. Our experimental and computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages.

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Baby’s First Bacteria: Discriminating Colonizing Commensals from Pathogens.

At birth, microbes rapidly colonize our epithelial surfaces. In this issue of Cell Host & Microbe, Leech et al. (2019) uncover how the neonatal immune system discriminates between a colonizing commensal and pathogen to selectively generate tolerance to commensal species.

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Epidermal development, growth control, and homeostasis in the face of centrosome amplification

Kulukian A, Vitre B, Holland A, Naik S, Cleveland D, Fuchs E. Epidermal development, growth control, and homeostasis in the face of centrosome amplification. Proceedings of the National Academy of Sciences. 112(46):E6311-E6320 Nov, 2015

The full extent to which centrosome amplification might directly contribute to human disease is poorly understood.  Our findings challenge the role for centrosome amplification in the initiation of skin tumorigenesis and demonstrate that certain tissues are better able to cope with its burden.

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The transcriptional factors Thpok and LRF are redundantly necessary for helper T cell differentiation.

Carpenter A, Grainger JR, Xiong Y, Chu HH, Wang L, Naik S, Dos Santos L, Wei L, Jenkins MK, O’Shea J, Belkaid Y, Bosselut R. The transcriptional factors Thpok and LRF are redundantly necessary for helper T cell differentiation. Immunity. 37(4):622-33 Oct, 2012

T helper (Th) cells are critical for defenses against infection and recognize peptides bound to class II major histocompatibility complex (MHC II) molecules. Although transcription factorshave been identified that direct Th cells into specific effector fates, whether a “master” regulator controls the developmental program common to all Th cells remains unclear. Here, we showed that the two transcription factors Thpok and LRF share this function.

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