Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

Levi, Sonia; Taveggia, Carla

doi:10.1089/ars.2013.5813

Cited by 33 publications

(26 citation statements)

References 161 publications

(168 reference statements)

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“…Iron overload is mainly caused by certain genetic diseases and high‐iron diets. Excessive iron accumulation in the body can cause liver damage, cardiovascular damage, neurodegenerative diseases and many aging‐related diseases [21]. Iron overload has a profound effect on immature hematopoietic cells and stromal cells, and thereby destroys the hematopoietic process [22].…”

Section: Discussionmentioning

confidence: 99%

Iron overload inhibits self‐renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species

Han

Chen

et al. 2020

FEBS Open Bio

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Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ferric ammonium citrate (FAC) in a concentration‐dependent manner. In addition, deferoxamine protected hESCs/hiPSCs against FAC‐induced cell‐cycle arrest. However, iron overload did not affect pluripotency in hESCs/hiPSCs. Further, treatment of hiPSCs with FAC resulted in excess reactive oxygen species production and DNA damage. Collectively, our findings provide new insights into the role of iron homeostasis in the maintenance of self‐renewal in human pluripotent stem cells.

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Section: Discussionmentioning

confidence: 99%

Iron overload inhibits self‐renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species

Han

Chen

et al. 2020

FEBS Open Bio

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“…We next screened for transcripts not previously described in mySCs or in PNS myelination (SI Appendix, Table S4). Such "new-in-mySC" transcripts included metallothioneins (Mt1 and Mt2) and a ferritin chain gene (Fth1) with metal transport and antioxidant functions and unknown relevance in the PNS (18). Also, the transcription factor Btg2 was not previously described in mySCs.…”

Section: Detailed Transcriptomic Characterization Of Schwann Cell Andmentioning

confidence: 99%

Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity

Wolbert

Heming

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

110

143

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Peripheral nerves contain axons and their enwrapping glia cells named Schwann cells (SCs) that are either myelinating (mySCs) or nonmyelinating (nmSCs). Our understanding of other cells in the peripheral nervous system (PNS) remains limited. Here, we provide an unbiased single cell transcriptomic characterization of the nondiseased rodent PNS. We identified and independently confirmed markers of previously underappreciated nmSCs and nerve-associated fibroblasts. We also found and characterized two distinct populations of nerve-resident homeostatic myeloid cells that transcriptionally differed from central nervous system microglia. In a model of chronic autoimmune neuritis, homeostatic myeloid cells were outnumbered by infiltrating lymphocytes which modulated the local cell–cell interactome and induced a specific transcriptional response in glia cells. This response was partially shared between the peripheral and central nervous system glia, indicating common immunological features across different parts of the nervous system. Our study thus identifies subtypes and cell-type markers of PNS cells and a partially conserved autoimmunity module induced in glia cells.

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“…Iron homeostasis plays an important role in a wide range of cellular activities, including proliferation, cell cycle, programmed cell death, and development . Also, it is important to keep iron homeostasis for maintaining the normal structure and function of the brain, nerves, heart, liver, and other organs . The disturbance of iron homeostasis has been shown to be associated with a variety of pathological conditions, such as anemia, tumors, heart failure, aging, and neurodegeneration .…”

Section: Introductionmentioning

confidence: 99%

Iron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids-Epigenetic Circuit

Han

et al. 2019

Stem Cells

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Iron homeostasis is crucial for a variety of biological processes, but the biological role of iron homeostasis in pluripotent stem cells (PSCs) remains largely unknown. The present study aimed to determine whether iron homeostasis is involved in maintaining the pluripotency of human PSCs (hPSCs). We found that the intracellular depletion of iron leads to a rapid downregulation of NANOG and a dramatic decrease in the self-renewal of hPSCs as well as spontaneous and nonspecific differentiation. Moreover, long-term depletion of iron can result in the remarkable cell death of hPSCs via apoptosis and necrosis pathways. Additionally, we found that the depletion of iron increased the activity of lipoprotein-associated phospholipase A2 (LP-PLA2) and the production of lysophosphatidylcholine, thereby suppressing NANOG expression by enhancer of zeste homolog 2-mediated trimethylation of histone H3 lysine 27. Consistently, LP-PLA2 inhibition abrogated iron depletion-induced loss of pluripotency and differentiation. Altogether, the findings of our study demonstrates that iron homeostasis, acting through glycerophospholipid metabolic pathway, is essential for the pluripotency and survival of hPSCs. STEM CELLS 2019;37:489-503 SIGNIFICANCE STATEMENTIron homeostasis is essential for various biological processes. In this study, it was first demonstrated that iron deficiency could severely impair the pluripotency and differentiation of hESCs/ hiPSCs through the downregulation of NANOG by LysoPC-mediated H3K27me3. In addition, long-term iron deficiency reduced the survival and promoted apoptosis in hESCs/hiPSCs. Findings provide novel insights into the underlying mechanisms of iron homeostasis in maintaining the pluripotency and self-renewal of hESCs/hiPSCs

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Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

Cited by 33 publications

References 161 publications

Iron overload inhibits self‐renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species

Iron overload inhibits self‐renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species

Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity

Iron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids-Epigenetic Circuit

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