Stem cells and the impact of ROS signaling

Bigarella, Carolina L.; Liang, Raymond; Ghaffari, Saghi

doi:10.1242/dev.107086

Cited by 531 publications

(507 citation statements)

References 178 publications

Supporting

Mentioning

474

Contrasting

Unclassified

Order By: Relevance

“…ROS are well known to have diverse biological consequences, which are tissue specific. [54][55][56][57] ROS has also been implicated previously as a determinant of MSC behavior [58][59][60][61] in cancer patients. We document that a ROS inhibitor not only blocked BM MSC proliferation but also reduced the expression of genes associated with osteoblastic differentiation.…”

Section: Discussionmentioning

confidence: 90%

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lü

Xia

Liu

et al. 2015

Blood

View full text Add to dashboard Cite

Key Points• LCN2 acts to generate reactive oxygen species, leading to increased DNA strand breaks and apoptosis in normal CD34 1 cells.• LCN2 promotes the generation of osteoblasts but diminishes adipogenesis, resembling the composition of the MF marrow microenvironment.Myelofibrosis (MF) is characterized by cytopenias, constitutional symptoms, splenomegaly, and marrow histopathological abnormalities (fibrosis, increased microvessel density, and osteosclerosis). The microenvironmental abnormalities are likely a consequence of the elaboration of a variety of inflammatory cytokines generated by malignant megakaryocytes and monocytes. We observed that levels of a specific inflammatory cytokine, lipocalin-2 (LCN2), were elevated in the plasmas of patients with myeloproliferative neoplasms (MF > polycythemia vera or essential thrombocythemia) and that LCN2 was elaborated by MF myeloid cells. LCN2 generates increased reactive oxygen species, leading to increased DNA strand breaks and apoptosis of normal, but not MF, CD34 1 cells. Furthermore, incubation of marrow adherent cells or mesenchymal stem cells with LCN2 increased the generation of osteoblasts and fibroblasts, but not adipocytes. LCN2 priming of mesenchymal stem cells resulted in the upregulation of RUNX2 gene as well as other genes that are capable of further affecting osteoblastogenesis, angiogenesis, and the deposition of matrix proteins. These data indicate that LCN2 is an additional MF inflammatory cytokine that likely contributes to the creation of a cascade of events that results in not only a predominance of the MF clone but also a dysfunctional microenvironment. (Blood. 2015;126(8):972-982)

show abstract

Section: Discussionmentioning

confidence: 90%

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lü

Xia

Liu

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

“…Physiological redox transitions required for stem cell differentiation and gene expression during embryonic development (30,31) may also be sensed by TRPM7 and transduced via Zn -dependent signals (32). Because TRPM7 patch-clamp recording is limited to the plasma membrane, the assumption has been that TRPM7's main function is on the plasma membrane.…”

Section: +mentioning

confidence: 99%

TRPM7 senses oxidative stress to release Zn ²⁺ from unique intracellular vesicles

Abiria

Krapivinsky

Sah

et al. 2017

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

102

View full text Add to dashboard Cite

TRPM7 (transient receptor potential cation channel subfamily M member 7) regulates gene expression and stress-induced cytotoxicity and is required in early embryogenesis through organ development. Here, we show that the majority of TRPM7 is localized in abundant intracellular vesicles. These vesicles (M7Vs) are distinct from endosomes, lysosomes, and other familiar vesicles or organelles. , an ion channel and cytoplasmic kinase, is ubiquitously expressed and essential in early embryonic development (1-4) but also may mediate oxidative stress-induced anoxic neuronal death in adults (5, 6). As an ion channel, TRPM7 conducts Zn 2+ >Mg 2+ ∼ Ca 2+ and monovalent cations (7-10) and contributes to labile cytosolic and nuclear Zn 2+ concentrations (8). TRPM7's C-terminal kinase can phosphorylate multiple substrates (11-13) and is cleaved to release a proapoptotic, chromatin-modifying enzyme (8,14). Zn 2+ regulates TRPM7's kinase activity (11) and binding to transcription factors (8). It is a potent signal for many cellular processes previously related to TRPM7 function, including gene expression, mitosis, and cell survival, but is also proapoptotic at extreme concentrations (15)(16)(17)(18) Oxidative stress increases inward divalent ion permeation through TRPM7 (5, 9), whereas acute and chronic oxidative stress in culture (24-26) or during ischemia-reperfusion in vivo (27, 28) induces TRPM7 expression. The resulting increase in cytosolic Zn 2+ could result in toxic cytosolic concentrations (9). Conversely, reduction of TRPM7 expression protects animals from postischemia reperfusion (5), a condition typically accompanied by increased reactive oxygen species (ROS) and Zn 2+ release from intracellular stores (29). Physiological redox transitions required for stem cell differentiation and gene expression during embryonic development (30, 31) may also be sensed by TRPM7 and transduced via Zn -dependent signals (32). Because TRPM7 patch-clamp recording is limited to the plasma membrane, the assumption has been that TRPM7's main function is on the plasma membrane. However, we have previously shown that TRPM7 is also on intracellular membranes (33-35). Indeed, ROS activation of divalent ion influx through TRPM7 (5, 9) is reminiscent of ROS activation of TRPM2, which releases Ca 2+ and Zn 2+ from lysosomes (36,37 ] and ROS during development and injury.

show abstract

“…The accumulation of damaged DNA compromises the genomic stability of hematopoietic stem cells (HSC) 5 (1) and may promote hematological malignancies, specifically with age (2,3). Reactive oxygen species (ROS) are one of the major insults that induce DNA damage (4), including in normal hematopoietic and leukemic stem cells.…”

mentioning

confidence: 99%

FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage

Bigarella

Rimmelé

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Edited by Xiao-Fan WangAccumulation of damaged DNA in hematopoietic stem cells (HSC) is associated with chromosomal abnormalities, genomic instability, and HSC aging and might promote hematological malignancies with age. Despite this, the regulatory pathways implicated in the HSC DNA damage response have not been fully elucidated. One of the sources of DNA damage is reactive oxygen species (ROS) generated by both exogenous and endogenous insults. Balancing ROS levels in HSC requires FOXO3, which is an essential transcription factor for HSC maintenance implicated in HSC aging. Elevated ROS levels result in defective

show abstract

Stem cells and the impact of ROS signaling

Cited by 531 publications

References 178 publications

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

TRPM7 senses oxidative stress to release Zn ²⁺ from unique intracellular vesicles

FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage

Contact Info

Product

Resources

About

Stem cells and the impact of ROS signaling

Cited by 531 publications

References 178 publications

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

TRPM7 senses oxidative stress to release Zn 2+ from unique intracellular vesicles

FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage

Contact Info

Product

Resources

About

TRPM7 senses oxidative stress to release Zn ²⁺ from unique intracellular vesicles