Publications by authors named "Michihiro Hashimoto"
Article Synopsis
- The study focuses on how chromatin structure changes during the development of multicellular organisms and highlights the role of histone variants in cell differentiation.
- Researchers created knock-in mice with a FLAG tag on a testis-specific histone variant called H3t to better understand its function in vivo.
- Through immunostaining and mass spectrometry, they found that H3t-FLAG was present in spermatogonia and meiotic cells, showing similarities and differences in posttranslational modifications compared to the standard histone H3.
Article Synopsis
- The study explores how MITOL, an E3 ubiquitin ligase, influences hematopoietic stem cell (HSC) maintenance and function in the bone marrow.
- Researchers created mice with a specific knockout of the Mitol gene, finding that the absence of MITOL led to HSC exhaustion and impaired blood regeneration.
- The deletion of MITOL caused prolonged endoplasmic reticulum (ER) stress, triggering cell death in HSCs, though it did not significantly harm mitochondrial function; inhibiting IRE1α, a stress signaling pathway, partially prevented this cell death.
Article Synopsis
- Hematopoietic stem cells (HSCs) develop from blood vessel walls and circulate in newborns, but how they migrate into bone marrow is not well understood.
- This study utilizes a new intravital imaging method to observe neonatal HSCs labeled with a specific marker in their bone marrow niche, focusing on the tibia to avoid damaging fragile bones.
- Findings show that neonatal HSCs migrate faster than adult HSCs, moving through bone-penetrating blood vessels and eventually settling in the bone marrow.
In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic recovery remain unclear. We herein provide novel insights into HSC regulation during regeneration by focusing on mitochondrial metabolism and ATP citrate lyase (ACLY).
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- Thermogenic brown and beige fat cells play a crucial role in regulating energy metabolism and protecting against obesity and related diseases by expressing uncoupling protein 1 (UCP1).* -
- The study explored how administering Cellular repressor of E1A-stimulated genes 1 (CREG1) affects UCP1 and diet-induced obesity (DIO) in mice at a comfortable temperature of 30°C, leading to increased UCP1 levels and reduced body fat.* -
- Results showed that CREG1 treatment boosted energy metabolism and fat browning in mice, but this effect was absent in UCP1-knockout mice, highlighting the essential role of UCP1 in combating obesity through CREG
Cellular senescence underlies tissue aging and aging-associated pathologies, as well as lung pathology. We and others have shown that elimination of senescent cells alleviates pulmonary diseases such as fibrosis and emphysema in animal models. We herein describe a protocol for assessing senescence-dependent lung phenotypes in mice.
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- Brown and beige adipocytes, which express UCP1, can enhance glucose and lipid metabolism, helping combat obesity and related conditions like type 2 diabetes.
- CREG1 overexpression aids in browning fat tissue and reduces diet-induced obesity in mice, suggesting a potential therapeutic role for obesity management.
- Administering recombinant CREG1 protein boosts UCP1 expression and improves metabolic health, while Creg1-expressing adenovirus promotes beige adipocyte gene expression, indicating CREG1's effectiveness in promoting beneficial fat tissue changes.
Article Synopsis
- Hematopoietic stem cells (HSCs) are critical for lifelong blood production and can either self-renew or differentiate; their quiescent state is linked to low mitochondrial activity.
- Recent research suggests that autophagy helps maintain HSC quiescence by reducing mitochondrial metabolism, but its role in neonatal HSCs— which actively divide— is not well understood.
- This study found that while autophagy-related gene 7 (Atg7) deficiency in neonatal HSCs leads to increased divisions and mitochondrial activity, it does not significantly impact their blood-forming ability or metabolic state, indicating that autophagy is not essential for HSC function during the neonatal stage.
Article Synopsis
- CREG1 is a secreted glycoprotein that promotes cellular senescence and has been linked to increased brown fat formation in transgenic mice.
- In a study, CREG1 was found to improve age-related metabolic issues like obesity and renal dysfunction in older transgenic mice compared to wild-type mice.
- The study suggests that elevated CREG1 levels could help alleviate kidney aging and dysfunction by reducing certain senescence-related markers and improving kidney structure and function.
An antioxidant suppressed lung cellular senescence and enhanced pulmonary function in aged mice.
Biochem Biophys Res Commun
February 2021
Oxidative stress is one of the major causes of cellular senescence in mammalian cells. The excess amount of reactive oxygen species generated by oxygen metabolism is pathogenic and facilitates tissue aging. Lung tissue is more susceptible to oxidative stress than other organs because it is directly exposed to environmental stresses.
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- The tumor suppressor folliculin (FLCN) regulates the movement of TFE3, a key transcription factor for lysosome production, by controlling Rag GTPases related to amino acid sensing.
- In mice with a specific deletion of Flcn in blood cell lineage, researchers observed an increase in unhealthy phagocytes that resembled symptoms of lysosomal storage disorders (LSD).
- The study suggests that FLCN and TFE3 work in a feedback loop to manage lysosomal function, where FLCN loss increases TFE3 activity, leading to enhanced glycogenesis and abnormal phagocyte behavior; deleting TFE3 in Flcn-deficient mice can reduce these negative effects.
Article Synopsis
- HSCs (hematopoietic stem cells) can be categorized by the amount of mitochondria they contain, which is referred to as mitochondrial mass.
- Cells with a higher mitochondrial mass are typically in a quiescent state, meaning they are not actively dividing or differentiating.
- Additionally, these high mitochondrial mass HSCs demonstrate a greater ability to reconstitute or restore the blood system when needed.
Article Synopsis
- Monocyte-derived fibrocytes play a significant role in the pathogenesis of myelofibrosis (MF), with findings indicating that serum amyloid P can suppress their differentiation and improve MF outcomes.
- The study revealed that MPN patients with MF and the V617F mutation have a higher percentage of SLAMF7 monocytes, and this is positively correlated with the severity of the mutation and levels of interleukin-1ra (IL-1ra).
- Elotuzumab (Elo), an anti-SLAMF7 antibody, shows promise as a potential treatment for MF by independently inhibiting fibrocyte differentiation and alleviating associated symptoms in preclinical models.
Article Synopsis
- In Bacillus subtilis, ECF sigma factors are activated when there's decreased phosphatidylglycerol (PG) or the absence of glucolipids and lipoteichoic acid (LTA).
- The study investigates whether these changes independently cause activation of ECF sigma factors, with an emphasis on the role of glucolipids and PG.
- Results showed that disruptions in glucolipid synthesis and reduction of PG both led to increased activation levels of several ECF sigma factors, indicating these factors regulate independently of any changes in LTA.
Increased formation of brown and beige adipocytes is critical for adaptive thermogenesis to maintain homeothermy in cold or to circumvent diet-induced obesity (DIO). Cellular repressor of adenovirus early region 1A-stimulated genes 1 (CREG1) exhibits the ability to stimulate brown adipogenesis, including the induction of uncoupling protein 1 (UCP1), . Thus, we aimed to clarify whether CREG1 promotes brown adipocyte formation and inhibits DIO at the whole-animal level.
View Article and Find Full Text PDFErythropoiesis is a highly coordinated stepwise process involving the progressive clearance of mitochondria via mitophagy. Based on the expression of several macroautophagy and mitophagy specific genes, we identified a sequential change in the transcriptional pattern during terminal erythroid differentiation. Because erythroid cells are a major source of serum sphingosine-1-phosphate, we analyzed the role of sphingolipid signaling in erythropoiesis and demonstrate that sphingosine kinase activity promotes terminal erythroid differentiation by regulating the expression of key mitophagy genes Pink1 and Bnip3l/Nix.
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- - CREG1 is important for brown adipogenesis and regulates UCP1, a protein crucial for burning fat and generating heat, particularly in cold conditions or during obesity.
- - In a study using murine stem cells, higher levels of CREG1 led to increased expression of brown fat-related genes, while suppressing CREG1 decreased their expression.
- - CREG1 also aids in brown fat formation even without thyroid hormone, suggesting it works with other factors like retinoic acid to enhance UCP1 expression and help combat obesity.
Article Synopsis
- Most hematopoietic stem cells (HSCs) in the bone marrow are in a quiescent state with low mitochondrial activity, but they begin to divide under stress conditions such as chemotherapy with 5-fluoruracil (5-FU).
- Research revealed that HSCs start dividing after increased mitochondrial membrane potential (ΔΨ) due to higher intracellular calcium levels.
- Modulating calcium levels using adenosine or a calcium channel blocker like Nifedipine can extend the time between HSC divisions while also maintaining their population, highlighting the pivotal role of the calcium-mitochondria pathway in determining HSC fate.
Article Synopsis
- Osteoclast differentiation involves significant changes in metabolism and gene expression, and recent research highlights the link between these processes during osteoclast development.
- Researchers found that deleting the tumor suppressor gene Folliculin (Flcn) in mouse osteoclast precursors leads to rapid osteoporosis due to excessive osteoclast formation.
- Flcn plays a crucial role in controlling energy production and purine metabolism, influencing a signaling pathway that can be targeted to prevent accelerated osteoclast growth in the absence of this gene.
Article Synopsis
- * The study reveals that integrin αvβ3 plays a crucial role in HSC behavior, particularly by negatively regulating HSC function in the presence of the inflammatory cytokine interferon-γ (IFNγ).
- * Integrin β3 signaling enhances the effects of IFNγ on HSCs by promoting specific gene expression, highlighting how cell adhesion can modulate HSC activity during normal and inflammatory states.
Article Synopsis
- Senescent cells accumulate with age and are linked to various age-related health issues, mainly due to the actions of tumor suppressors p19 and p16 that induce permanent cell cycle arrest.
- Eliminating p16-expressing cells has been shown to extend mouse lifespan, but it’s unclear if removing senescent cells restores tissue function or how p19 affects aging.
- A study found that removing p19-expressing cells in 12-month-old mice can reversibly restore lung function and reverse aging-related gene expression changes, suggesting p19 plays a significant role in lung function decline with age.
Tunneling nanotubes (TNTs), the long membrane extensions connecting distant cells, have emerged as a novel form of cell-to-cell communication. However, it is not fully understood how and to what extent TNTs contribute to intercellular spread of pathogens including HIV-1. In this study, we show that HIV-1 promotes TNT formation per se via its protein Nef and a cellular protein M-Sec, which appears to mediate approximately half of viral spread among monocyte-derived macrophages (MDMs).
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- * This study reveals that differentiated fibrocytes can be infected by HIV-1 and exhibit a distinct, persistently infected phenotype, more so than macrophages.
- * The research indicates fibrocytes produce active HIV-1 while resisting cell death, suggesting they could serve as long-lived reservoirs for the virus, highlighting their potential importance in strategies aimed at curing HIV-1.
Extracytoplasmic function (ECF) σ factors respond to environmental stresses and regulate numerous genes required for adaptation. Under normal growth conditions, the ECF σ factors are sequestered by transmembrane anti-σ factor proteins, from which they are released under stress conditions. In Bacillus subtilis ugtP null mutant cells, which lack glucolipids, three of the seven ECF σ factors, σM, σV and σX, are activated.
View Article and Find Full Text PDFBackground: HuR (human antigen R) is a ubiquitously expressed member of the Hu/ELAV family of proteins that is involved in diverse biological processes. HuR has also been shown to play an important role in cell cycle arrest during replicative senescence in both human and mouse cells. Senescent cells not only halt their proliferation, but also activate the secretion of proinflammatory cytokines.
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