ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal

Morimoto, Hiroko; Iwata, Kazuo; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Kanatsu-Shinohara, Mito; Morimoto, Takeshi; Yabe‐Nishimura, Chihiro; Shinohara, Takashi

doi:10.1016/j.stem.2013.04.001

Cited by 206 publications

(193 citation statements)

References 45 publications

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“…ROS generated by NADPH oxidases are also important for the self-renewal of spermatogonial stem cells (SSCs). However, elevated ROS in MSCs reduce their engraftment potential and induce apoptosis after transplantation (Morimoto et al, 2013;Rodrigues et al, 2012).…”

Section: ) the Defective Atmmentioning

confidence: 99%

Stem cells and the impact of ROS signaling

2014

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An appropriate balance between self-renewal and differentiation is crucial for stem cell function during both early development and tissue homeostasis throughout life. Recent evidence from both pluripotent embryonic and adult stem cell studies suggests that this balance is partly regulated by reactive oxygen species (ROS), which, in synchrony with metabolism, mediate the cellular redox state. In this Primer, we summarize what ROS are and how they are generated in the cell, as well as their downstream molecular targets. We then review recent findings that provide molecular insights into how ROS signaling can influence stem cell homeostasis and lineage commitment, and discuss the implications of this for reprogramming and stem cell ageing. We conclude that ROS signaling is an emerging key regulator of multiple stem cell populations.

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Section: ) the Defective Atmmentioning

confidence: 99%

Stem cells and the impact of ROS signaling

2014

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“…Recent evidence suggests that oxygen has two distinct effects on spermatogenesis; whereas oxidative stress is generally thought to cause male infertility, reactive oxygen species (ROS) have been shown to be required for the self-renewal of SSCs and the fertility of sperm (Agarwal et al, 2008;Morimoto et al, 2013). To begin dissecting the roles of oxygen concentration in spermatogenetic processes, we compared the efficiency of SSC differentiation under normal and low oxygen concentrations.…”

Section: Effect Of Oxygen On the Differentiation Of Sscs To Spermmentioning

confidence: 99%

Differentiation of zebrafish spermatogonial stem cells to functional sperm in culture

2015

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Molecular dissection and chemical screening on a complex process such as spermatogenesis could be facilitated by cell culture approaches that allow easy access for experimental manipulation and live imaging of specific molecules; however, technical limitations have thus far prevented the complete reconstruction of spermatogenic events in cell culture. Here, we describe the production of functional sperm from self-renewing spermatogonial stem cells (SSCs) in cell culture conditions, using zebrafish testicular hyperplasia cells that accumulate early stage spermatogonia. By serially transplanting hyperplasias into immunodeficient rag1 mutant zebrafish, we succeeded in long-term maintenance and efficient production of starting material for SSC culture. Through improvements of culture conditions, we achieved efficient propagation of SSCs derived from the hyperplasia. When SSCs that underwent the SSC-propagating step for 1 month were transferred onto Sertoli feeder cells, they differentiated into functional sperm that gave rise to offspring. Oxygen at the concentration of air proved to be detrimental for sperm differentiation from SSCs, but not for propagation of SSCs. These results indicate that the whole spermatogenic process can be represented in cell culture in zebrafish, facilitating analyses of the molecular mechanisms of spermatogenesis in vertebrates.

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“…Consistent with enhanced platelet production, reticulated platelets determined by thiazole orange staining were increased by 1.5-fold in these mice after analysis by flow cytometry ( Figure 3E). hematopoietic progenitors including cellular proliferation, [16][17][18][19] and porphyrin accumulation is a key feature of highly proliferating tumor cells, 20,21 we next performed a megakaryocyte-colony-forming unit assay to assess megakaryopoiesis in presence or absence of the antioxidant glutathione. The 1.5-fold increase in the number of megakaryocyte colonies in Abcb6 −/− BM was partially reversed by the addition of glutathione ( Figure 3G), providing evidence that ROS contributes to the enhanced proliferation.…”

Section: Lack Of Abcb6 Increases Mkp Proliferation and Platelet Expanmentioning

confidence: 99%

Deficiency of ATP-Binding Cassette Transporter B6 in Megakaryocyte Progenitors Accelerates Atherosclerosis in Mice

Murphy

Sarrazy

Wang

et al. 2014

ATVB

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Objective-The ATP-binding cassette (ABC) transporter B6 (ABCB6) is highly expressed in megakaryocyte progenitors, but its role in platelet production and disease has not been elucidated. Approach and Results-Among various ABC transporters, ABCB6 was highly expressed in megakaryocyte progenitors, exhibiting the same pattern of expression of genes involved in heme synthesis pathway. Transplantation of Abcb6 deficient (Abcb6) bone marrow into low density lipoprotein receptor deficient recipient mice resulted in expansion and proliferation of megakaryocyte progenitors, attributable to increased reactive oxygen species production in response to porphyrin loading. The enhanced megakaryopoiesis in Abcb6 −/− bone marrow-transplanted mice was further illustrated by increased platelet counts, mean platelet volume, and platelet activity. Platelets from Abcb6 −/− bone marrow-transplanted mice had higher levels of chemokine (C-C motif) ligand 5, which was associated with increased plasma chemokine (C-C motif) ligand 5 levels. There were also increased platelet-leukocyte aggregates, which resulted in leukocyte activation. Abcb6 −/− bone marrow-transplanted mice had accelerated atherosclerosis which was associated with deposition of the chemotactic agent, chemokine (C-C motif) ligand 5 in atherosclerotic plaques, resulting in increased macrophage accumulation. Conclusions-Our

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ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal

Cited by 206 publications

References 45 publications

Stem cells and the impact of ROS signaling

Stem cells and the impact of ROS signaling

Differentiation of zebrafish spermatogonial stem cells to functional sperm in culture

Deficiency of ATP-Binding Cassette Transporter B6 in Megakaryocyte Progenitors Accelerates Atherosclerosis in Mice

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