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

Naik, Shruti; Larsen, Samantha B.; Cowley, Christopher; Fuchs, Elaine

doi:10.1016/j.cell.2018.08.071

Cited by 205 publications

(161 citation statements)

References 93 publications

(152 reference statements)

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“…It is therefore not surprising that quiescence (as well as Gpha2 expression) is lost ex vivo, whereas culture conditions are sub-optimal and lacking essential components of the niche. The co-localization of T cells with qLSC strongly implies that these cells may secret cytokines to control LSC quiescence, in line with previous studies where immune cells were identified as niche cells for epithelial SCs 88 . In the clinics, corticosteroids such as dexamethasone are being widely used to prevent uncontrolled corneal inflammation and neo-vascularisation, as these agents are considered as highly effective drugs for nonspecific suppression of inflammation.…”

Section: Discussionsupporting

confidence: 88%

Capturing limbal epithelial stem cell population dynamics, signature, and their niche

Altshuler

Amitai-Lange

Tarazi

et al. 2020

Preprint

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AbstractStem cells (SCs) are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. It was several decades ago, when limbal epithelial SCs (LSCs) that regenerate the corneal epithelium were one of the first sporadic, quiescent SCs ever discovered. However, LSC dynamics, heterogeneity and genetic signature are largely unknown. Moreover, recent accumulating evidence strongly suggested that epithelial SCs are actually abundant, frequently dividing cells that display stochastic behavior.In this work, we performed an in-depth analysis of the murine limbal epithelium by single-cell RNA sequencing and quantitative lineage tracing. The generated data provided an atlas of cell states of the corneal epithelial lineage, and particularly, revealed the co-existence of two novel LSC populations that reside in separate and well-defined sub-compartments. In the “outer” limbus, we identified a primitive widespread population of quiescent LSCs (qLSCs) that uniformly express Krt15/Gpha2/Ifitm3/Cd63 proteins, while the “inner” limbus host prevalent active LSCs (aLSCs) co-expressing Krt15-GFP/Atf3/Mt1-2/Socs3. Analysis of LSC population dynamics suggests that while qLSCs and aLSCs possess different proliferation rates, they both follow similar stochastic rules that dictate their self-renewal and differentiation. Finally, T cells were distributed in close proximity to qLSCs. Indeed, their absence or inhibition resulted in the loss of quiescence and delayed wound healing. Taken together, we propose that divergent regenerative strategies are tailored to properly support tissue-specific physiological constraints. The present study suggests that in the case of the cornea, quiescent epithelial SCs are abundant, follow stochastic rules and neutral drift dynamics.

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Section: Discussionsupporting

confidence: 88%

Capturing limbal epithelial stem cell population dynamics, signature, and their niche

Altshuler

Amitai-Lange

Tarazi

et al. 2020

Preprint

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“…In addition, phagocytosis of newborn cells has also been recently shown to play a role in sculpting sex differences in the developing amygdala (VanRyzin et al, 2019). While previous work has suggested a largely detrimental effect of microglia on hippocampal neurogenesis (Valero et al, 2016), our data are in agreement with recent evidences supporting the essential role of macrophages and other immune cells in remodeling stem cells niches (Naik et al, 2018).…”

Section: Phagocytosis Reprograms Microgliasupporting

confidence: 92%

Microglia actively remodels adult hippocampal neurogenesis through the phagocytosis secretome

Díaz-Aparicio

Paris

Sierra-Torre

et al. 2019

Preprint

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words)During adult hippocampal neurogenesis, the majority of newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of their intracellular contents. Here, we propose that phagocytosis is not merely a passive process of corpse removal but has an active role in maintaining adult hippocampal neurogenesis. First, we found that neurogenesis was disrupted in mice chronically deficient for two microglial phagocytosis pathways (P2Y12 and MerTK/Axl), but was transiently increased in mice in which MerTK expression was conditionally downregulated. Next, we performed a transcriptomic analysis of microglial phagocytosis in vitro and identified genes involved in metabolism, chromatin remodeling, and neurogenesis-related functions. Finally, we discovered that the secretome of phagocytic microglia limits the production of new neurons both in vivo and in vitro. Our data suggest that reprogrammed phagocytic microglia act as a sensor of local cell death, modulating the balance between cell proliferation and cell survival in the neurogenic niche, thereby supporting the long-term maintenance of adult hippocampal neurogenesis.

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“…Thus, through their ability to sense and respond to niche signals, stem cells can adjust to and survive stressful situations. Remarkably, stem cells form an enduring epigenetic memory from such encounters, which equips them with the ability to mobilize more rapidly during subsequent assaults 6,95 .…”

Section: Trained Immunity In Stromal and Epidermal Stem Cellsmentioning

confidence: 99%

Defining trained immunity and its role in health and disease

et al. 2020

Self Cite

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| Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity. ✉

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

Cited by 205 publications

References 93 publications

Capturing limbal epithelial stem cell population dynamics, signature, and their niche

Capturing limbal epithelial stem cell population dynamics, signature, and their niche

Microglia actively remodels adult hippocampal neurogenesis through the phagocytosis secretome

Defining trained immunity and its role in health and disease

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