GENES TO CELLS 为发表描述分子和细胞生物学重要方面的论文提供了一个国际论坛。该杂志旨在发表在相关领域提供概念性进展的论文。将特别强调旨在了解生物学事件的基本机制的工作。

Genes to Cells is an international forum dedicated to publishing important research papers in the field of molecular and cellular biology. The journal aims to present conceptual advancements in related areas, with a particular emphasis on studies that seek to understand the fundamental mechanisms underlying biological events.

《Genes to Cells》是一个国际论坛，专注于发表分子和细胞生物学领域的重要研究论文。该杂志旨在发布在相关领域内提供概念性进展的研究成果，特别强调揭示生物学事件基本机制的研究工作。

Genes to Cells

Glaucoma is a neurodegenerative disorder caused by the death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is a cause of glaucoma. However, glaucoma often develops with normal IOP and is known as normal-tension glaucoma (NTG). Glutamate neurotoxicity is considered as one of the significant causes of NTG, resulting in excessive stimulation of retinal neurons via the N-methyl-D-aspartate (NMDA) receptors. The present study examined the phosphorylation of collapsin response mediator protein-2 (CRMP2), a protein that is abundantly expressed in neurons and involved in their development. In two mouse models, NMDA-injection and glutamate/aspartate transporter (GLAST) mutant, CRMP2 phosphorylation at the cyclin-dependent kinase-5 (Cdk5) site was elevated in RGCs. We confirmed that the decrease in the number of RGCs and thickness of the inner retinal layer (IRL) could be suppressed after NMDA administration in CRMP2KI/KI mice with genetically inhibited CRMP2 phosphorylation. Next, we investigated GLAST heterozygotes (GLAST+/-) with CRMP2KI/KI (GLAST+/-;CRMP2KI/KI) and GLAST knockout (GLAST-/-) mice with CRMP2KI/KI (GLAST-/-;CRMP2KI/KI) mice and compared them with GLAST+/- and GLAST-/- mice. pCRMP2 (S522) inhibition significantly reduced RGC loss and IRL thinning. These results suggest that the inhibition of CRMP2 phosphorylation could be a novel strategy for treating NTG.

Musukha Mala Brahma

Kazuya Takahashi

Kazuhiko Namekata

Takayuki Harada

Yoshio Goshima

Toshio Ohshima

Genetic inhibition of collapsin response mediator protein‐2 phosphorylation ameliorates retinal ganglion cell death in normal‐tension glaucoma models

遗传抑制collapsin反应介质蛋白-2磷酸化改善正常眼压性青光眼模型中视网膜神经节细胞死亡

Background Within the basic region‐helix‐loop‐helix (bHLH)‐PAS family of transcription factors, Arnt and Arnt2 play unique roles; these two factors not only heterodimerize with themselves, but also with other members of this family and they act as transcription regulators which bind to specific DNA elements. Whereas Arnt is broadly expressed in various tissues, the expression of Arnt2 is known to be limited to the neural tissues. Results To elucidate the function of Arnt2 in detail, we cloned the mouse Arnt2 gene and its gene structure was determined. We subsequently generated germ line Arnt2 mutant mice by gene targeting technology. Heterozygous Arnt2 mice were viable, but homozygous Arnt2 gene knockout mice died shortly after birth. Histological and immunological analyses revealed that the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) are hypocellular. Moreover, secretory neurones identified by the expression of neurosecretory hormone such as arginine vasopressin, oxytocin, corticotrophin‐releasing hormone and somatostatin are completely absent in SON and PVN in the mutant Arnt2 mice. Consistent with these observations, prospective SON and PVN neurones which express Brn2 appeared around E13.5 in the mantle zone, but no neurones which expressed the neurosecretory hormones were found in the SON and PVN regions. Conclusions These data show that the transcription factor Arnt2 controls the development of the secretory neurones at the later or final stages of differentiation rather than at the beginning stage. Strikingly similar observations have been reported with the Sim1 deficient mice. Taken together, our results demonstrate that Arnt2 is an indispensable transcription factor for the development of the hypothalamus, and suggest that Arnt2 is an obligatory partner molecule of Sim1 in the developmental process of the neuroendocrinological cell lineages.

Tomonori Hosoya

Yoshihito Oda

Satoru Takahashi

Masanobu Morita

Shimako Kawauchi

Masatsugu Ema

Masayuki Yamamoto

Yoshiaki Fujii‐Kuriyama

Defective development of secretory neurones in the hypothalamus of Arnt2‐knockout mice

Abstract Bladder cancer is a urothelial cancer and effective therapeutic strategies for its advanced stages are limited. Here, we report that CD271, a neurotrophin receptor, promotes the proliferation and migration of bladder cancer cells. CD271 knockdown decreased proliferation in both adherent and spheroid cultures, and vice versa when CD271 was overexpressed in bladder cancer cell lines. CD271 depletion impaired tumorigenicity in vivo. Migration activity was reduced by CD271 knockdown and TAT‐Pep5, a known CD271‐Rho GDI‐binding inhibitor. Apoptosis was induced by CD271 knockdown. Comprehensive gene expression analysis revealed alterations in E2F‐ and Myc‐related pathways upon CD271 expression. In clinical cases, patients with high CD271 expression showed significantly shortened overall survival. In surgically resected specimens, pERK, a known player in proliferation signaling, colocalizes with CD271. These data indicate that CD271 is involved in bladder cancer malignancy by promoting cell proliferation and migration, resulting in poor prognosis.

Shingo Myoen

Mai Mochizuki

Rie Shibuya‐Takahashi

Haruna Fujimori

Norihisa Shindo

Kazunori Yamaguchi

Jun Yasuda

Jiro Abe

Takayuki Imai

Ikuro Sato

Hisanobu Adachi

Sadafumi Kawamura

Akihiro Ito

Keiichi Tamai

<scp>CD271</scp> promotes proliferation and migration in bladder cancer

Understanding the molecular genetic basis of animal magnet reception has been one of the big challenges in molecular biology. Recently it was discovered that the magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry). Here, using the fruit fly as a magnet-receptive model organism, we show that the magnetic field exposure (0.4-0.6 mT) extended lifespan under starvation, but not in cryptochrome mutant flies (cryb ). The magnetic field exposure increases motor function in wild type and neurodegenerative disease model flies. Furthermore, the magnetic field exposure improved sleep quality at night-time specific manner, but not in cryb . We also showed that repeated AC magnetic field exposure increased climbing activity in wild-type Drosophila, but not in cryb . The data suggests that magnetic field-dependent improvement of lifespan, sleep quality, and motor function is mediated through a cry-dependent pathway in Drosophila.

Haruhisa Kawasaki

Hideyuki Okano

Hiromi Ishiwatari

Tetsuo Kishi

Norio Ishida

A role of cryptochrome for magnetic field‐dependent improvement of sleep quality, lifespan, and motor function in Drosophila

The brain utilizes glucose as a primary energy substrate but also fatty acids for the β-oxidation in mitochondria. The β-oxidation is reported to occur mainly in astrocytes, but its capacity and efficacy against different fatty acids remain unknown. Here, we show the fatty acid preference for the β-oxidation in mitochondria of murine cultured astrocytes. Fatty acid oxidation assay using an extracellular flux analyzer showed that saturated or monosaturated fatty acids, palmitic acid and oleic acid, are preferred substrates over polyunsaturated fatty acids like arachidonic acid and docosahexaenoic acid. We also report that fatty acid binding proteins expressed in the astrocytes contribute less to fatty acid transport to mitochondria for β-oxidation. Our results could give insight into understanding energy metabolism through fatty acid consumption in the brain.

Laarni Grace Corales

Hitoshi Inada

Yuji Owada

Noriko Osumi

Fatty acid preference for beta‐oxidation in mitochondria of murine cultured astrocytes

小鼠培养星形胶质细胞线粒体中脂肪酸偏好于β-氧化

ABSTRACT Abnormalities in spermatogenesis, a fundamental component of male reproductive function, can cause male infertility. Somatic cells constituting the testis microenvironment are essential for controlling normal spermatogenesis. Although testicular somatic cells are thought to sense and respond to germ cells to ensure proper spermatogenesis, the details of this signaling mechanism are unknown. Here, we investigated somatic cell dynamics in testicular tissue lacking spermatogenesis using the mice with deletion of the testis‐specific histone H3 variant gene H3t . Testicular tissue sections of H3t Δ/Δ mice exhibited an increased interstitial area compared with those of wild‐type mice, which was primarily attributed to an increase in Leydig cell numbers. Furthermore, this increase in Leydig cells led to increased testosterone synthesis, which occurred alongside cellular senescence‐associated β‐galactosidase activity. These findings suggest that Leydig cells monitor the progress of spermatogenesis and possess a mechanism to promote functional germ cell formation.

Qianmei Wu

Miho Ito

Takeru Fujii

Kaori Tanaka

Kohta Nakatani

Yoshihiro Izumi

Takeshi Bamba

Takashi Baba

Kazumitsu Maehara

Kosuke Tomimatsu

Tatsuya Takemoto

Yasuyuki Ohkawa

Akihito Harada

Defects in the H3t Gene Cause an Increase in Leydig Cells With Impaired Spermatogenesis in Mice

H3t基因缺陷导致小鼠睾丸间质细胞增多及精子发生障碍

ABSTRACT Acute liver failure is a serious, life‐threatening disease. Although the gut microbiota has been considered to play a role in liver failure, the extent to which it is involved in the pathogenesis of this disease has not been fully elucidated to date. Therefore, we here analyzed the importance of the presence of intestinal microbiota in the pathogenesis of acute liver injury, using D‐galactosamine (D‐GalN)/lipopolysaccharide (LPS)‐treated mice, which is a widely used experimental model of acute liver injury. First, administration of the antibiotic polymyxin B markedly alleviated liver injury. Liver injury was also reduced in germ‐free mice, leading to the conclusion that the presence of intestinal microbiota aggravates D‐GalN/LPS‐induced liver injury. The amount of bacteria and LPS transferred from the gut to the blood was not increased by D‐GalN/LPS, suggesting that the worsening of liver injury was not simply owing to the entry of bacteria into the circulation. In conclusion, acute liver injury in polymyxin B‐pretreated or germ‐free mice was ameliorated by modulation of the gut microbiota. Modification of the gut microbiota using polymyxin B may hence have the potential to alleviate acute liver injury in human patients.

Kazuma Ohshima

Satoru Torii

Shigeomi Shimizu

Presence of Gut Microbiota Worsens D‐Galactosamine and Lipopolysaccharide‐Induced Hepatic Injury in Mice

肠道菌群的存在加重D-半乳糖胺和脂多糖诱导的小鼠肝损伤

ABSTRACT Schizophyllum commune , a common wood‐decay mushroom known for its extremely high genetic variation and as a rare cause of human respiratory diseases, could be a promising model fungus contributing to both biology and medicine. To better understand its phenotypic variation, we developed an image analysis system that quantifies morphological and physiological traits of mycelial colonies in Petri dishes. This study evaluated growth of six wild and one clinical isolates of Japanese S. commune , subjected to different temperatures and glucose concentrations, including a condition mimicking the human respiratory environment. Our analysis revealed that combinations of two growth indices, area and whiteness, and profiling by clustering algorithms highlighted strain‐specific responses. For example, the clinical isolate was the whitest under the respiratory‐like condition. We also found that the growth rate was strongly determined by glucose concentration, while the effects of temperature on growth varied among the strains, suggesting that while glucose preference is common in this species, responses to temperature differ between strains. This system showed sufficient sensitivity to detect variation in mycelial growth. Our study provides a key to unraveling morphological and physiological traits behind the high polymorphisms in S. commune , including the ability to colonize the human respiratory tract.

Hiromi Matsumae

Megumi Sudo

Tadashi Imanishi

Tsuyoshi Hosoya

Image Analysis Characterizes Phenotypic Variation in the Growth of Mushroom‐Forming Fungus Schizophyllum commune

图像分析揭示蘑菇形成真菌裂褶菌生长中的表型变异

ABSTRACT Missing an entire chromosome or chromosome arm in normal diploid cells has a deleterious impact on cell viability, which may contribute to the development of specific birth defects. Nevertheless, the effects of chromosome loss in human cells have remained unexplored due to the lack of suitable model systems. Here, we developed an efficient, selection‐free approach to generate partial monosomy in human induced pluripotent stem cells (iPSCs). The introduction of Cas9 proteins and a pair of gRNAs induces over megabase‐sized interstitial chromosomal deletions. Using human chromosome 21 (HSA21) as a model, partial monosomy 21q (PM21q) iPSC lines with deletions ranging from 4.5 to 27.9 Mb were isolated. A 33.6 Mb deletion, encompassing all protein‐coding genes on 21q, was also achieved, establishing the first 21q monosomy human iPSC line. Transcriptome and proteome analyses revealed that the abundances of mRNA and protein encoded by the majority of genes in the monosomic regions are half of the diploid expression level, indicating an absence of dosage compensation. The ability to generate customized partial monosomy cell lines on an isogenic, karyotypically normal background should facilitate the gain of novel insights into the impact of chromosome loss on cellular fitness.

Masaya Egawa

Narumi Uno

Rina Komazaki

Yusuke Ohkame

Kyotaro Yamazaki

Chihiro Yoshimatsu

Yuki Ishizu

Yusaku Okano

Hitomaru Miyamoto

Mitsuhiko Osaki

Teruhiko Suzuki

Kazuyoshi Hosomichi

Yasunori Aizawa

Yasuhiro Kazuki

Kazuma Tomizuka

Generation of Monosomy 21q Human <scp>iPS</scp> Cells by <scp>CRISPR</scp>/Cas9‐Mediated Interstitial Megabase Deletion

通过CRISPR/Cas9介导的中间兆碱基缺失生成21q单体人类iPS细胞

Abstract Completion of DNA replication before chromosome segregation is essential for the stable maintenance of the genome. Under replication stress, DNA synthesis may persist beyond S phase, especially in genomic regions that are difficult to proceed with the replication processes. Incomplete replication in mitosis emerges as non‐disjoined segment in mitotic chromosomes leading to anaphase bridges. The resulting chromosome rearrangements are not well characterized, however. Here, we report that incomplete replication due to SMC5/6 deficiency impairs sister chromatid disjunction at difficult‐to‐replicate regions, including common fragile sites. These non‐disjoined regions manifest as cytologically defined symmetric gaps, causing anaphase bridges. These bridges break at the gaps, leading to telomere loss, micronucleation, and fragmentation. Subsequently, fusions between telomere‐deficient chromosomes generate complex chromosomal rearrangements, including dicentric chromosomes, suggesting the occurrence of breakage‐fusion‐bridge cycle. Additionally, chromosomes in micronuclei were pulverized, indicative of chromothripsis. Our findings suggest that incomplete replication facilitates complex chromosomal rearrangements, which may contribute to genomic instability in human cancers.

Yoshiharu Kusano

Yasuha Kinugasa

Satoshi Tashiro

Toru Hirota

Chromosomal rearrangements associated with <scp>SMC5</scp>/6 deficiency in <scp>DNA</scp> replication

与<scp>SMC5</scp>/6缺陷相关的<scp>DNA</scp>复制中的染色体重排

Abbreviation	Genes Cells
Journal Impact	1.49
Quartiles(Global)	GENETICS & HEREDITY(Q4)

ISSN	1356-9597, 1365-2443
h-index	124

Publication Information	Publisher: Wiley-Blackwell Publishing Ltd，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1996，Proportion of original research papers: 95.00%，Self Citation Rate:0.00%， Gold OA Rate: 13.49%
Average review cycle	网友分享经验：平均3月
Average recruitment ratio	网友分享经验：约50%

Genes to Cells

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