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| Open AccessApoL6 associates with lipid droplets and disrupts Perilipin1-HSL interaction to inhibit lipolysis
Lipolysis in adipose tissue releases fatty acids during fasting. Here, authors show that ApoL6, a lipid droplet-associated protein, is specifically expressed in adipocytes upon feeding to inhibit lipolysis by directly interacting with Perilipin 1 to competitively inhibit Perilipin 1-HSL interaction.
- Yuhui Wang
- , Hai P. Nguyen
- & Hei S. Sul
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Article
| Open AccessAdipose-targeted triiodothyronine therapy counteracts obesity-related metabolic complications and atherosclerosis with negligible side effects
Although thyroid hormone (TH) has anti-obesity potential, systemic administration of TH causes severe adverse effects without obvious weight loss. Here, the authors show that adipose tissue-targeted delivery of TH with liposomes is a safe and efficient strategy to treat obesity and its related complications in mice.
- Kang Chen
- , Lai Yee Cheong
- & Aimin Xu
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Article
| Open AccessThe Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
Adipose tissue fibrosis is connected to obesity-related metabolic dysfunction. Qiu and colleagues discover that the Hippo pathway acts as a molecular switch in the initiation and development of adipose tissue fibrosis upon TGFβ stimulation.
- Hongyu Shen
- , Xun Huang
- & Yifu Qiu
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Article
| Open AccessBeiging of perivascular adipose tissue regulates its inflammation and vascular remodeling
Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, the authors show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response as a protective mechanism.
- Yusuke Adachi
- , Kazutaka Ueda
- & Issei Komuro
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Review Article
| Open AccessIdentification, discrimination and heterogeneity of fibroblasts
In this review, the authors look at how recent progress in single-cell transcriptomics complement and enrich the classical, largely morphological, portraits of fibroblasts. The detailed molecular information now available provides new insights into fibroblast identity, heterogeneity and function.
- Urban Lendahl
- , Lars Muhl
- & Christer Betsholtz
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Article
| Open AccessAdipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice
Obesity impairs regulation of adipocyte lipolysis, which contributes towards development of insulin resistance. Here the authors report that adipocyte Gq signaling functions as a regulator of lipolysis and systemic glucose and lipid homeostasis in mice, suggesting that agents able to stimulate this pathway may prove useful as antidiabetic drugs.
- Takefumi Kimura
- , Sai P. Pydi
- & Jürgen Wess
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Article
| Open AccessOsteoblast-derived vesicles induce a switch from bone-formation to bone-resorption in vivo
Bone remodeling involves a switch between bone formation and resorption, but the mechanisms is unclear. Here, the authors show that intercellular communication via extracellular vesicles secreted by mature osteoblasts is a key factor for the switching, via a microRNA-mediated mechanism.
- Maki Uenaka
- , Erika Yamashita
- & Masaru Ishii
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Article
| Open AccessA neomorphic variant in SP7 alters sequence specificity and causes a high-turnover bone disorder
SP7 is a transcription factor required for osteoblast differentiation and bone formation. A neomorphic mutation in SP7 was found to alter DNA binding specificity, causing a complex skeletal disorder in both mice and humans.
- Julian C. Lui
- , Adalbert Raimann
- & Jeffrey Baron
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Article
| Open AccessMacrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.
- Bingyang Dai
- , Jiankun Xu
- & Ling Qin
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Article
| Open AccessA propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex
Disruption of CREB/CRTC2, a key gluconeogenic transcriptional complex, has been shown to ameliorate insulin resistance in mice. Here, the authors show that the inhibitor artipllin C and the synthetic compound A57, which presents with higher inhibitory activity, improve insulin sensitivity in obese mice by inhibiting CREB-CRTC2 interaction.
- Yaqiong Chen
- , Jiang Wang
- & Yi Liu
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Article
| Open AccessPPARα−ACOT12 axis is responsible for maintaining cartilage homeostasis through modulating de novo lipogenesis
Increasing evidence suggested that dysregulation in lipid metabolism is linked to OA pathogenesis, but the underlying regulatory mechanism is not well understood. Here, the authors show that PPARα-ACOT12 signalling regulates cartilage homeostasis by regulating de novo lipogenesis in mice.
- Sujeong Park
- , In-Jeoung Baek
- & Eun-Jung Jin
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Article
| Open AccessBMP8 and activated brown adipose tissue in human newborns
Brown adipose tissue (BAT) in infants has been studied for more than a century, however, the knowledge about its physiological features is limited. Here, the authors investigate the link between BAT thermogenesis and the regulation of temperature in human new-borns with non-invasive infrared thermography.
- Adela Urisarri
- , Ismael González-García
- & Miguel López
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Article
| Open AccessRSPO3 is important for trabecular bone and fracture risk in mice and humans
Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here, the authors show that RSPO3 exerts an important role for vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
- Karin H. Nilsson
- , Petra Henning
- & Claes Ohlsson
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Article
| Open AccessSelenoprotein W ensures physiological bone remodeling by preventing hyperactivity of osteoclasts
Selenoproteins containing selenium have a variety of physiological functions including redox homeostasis and thyroid hormone metabolism. Here, the authors show that RANKL-dependent repression of selenoprotein W regulates cell fusion during osteoclast differentiation and bone remodelling in mice.
- Hyunsoo Kim
- , Kyunghee Lee
- & Daewon Jeong
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Article
| Open AccessEpidermal growth factor receptor signaling uncouples germ cells from the somatic follicular compartment at ovulation
Uncoupling of mature oocytes from somatic granulosa cells is required for their fertilization. Here the authors show that activation of EGFR signalling in granulosa cells during ovulation triggers ERK-dependent loss of filopodia oocyte adhesion, and Arp2/3 mediated retraction of granulosa cell filopodia.
- Laleh Abbassi
- , Stephany El-Hayek
- & Hugh J. Clarke
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Article
| Open AccessOsteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins
The innate immune system and inflammation modulate bone homeostasis through complex regulation of bone remodelling cells including osteoblasts and osteoclasts. Here, the authors show that the type I interferon pathway and guanylate binding proteins functionally limit bone loss by inhibiting osteoclast functions.
- David E. Place
- , R. K. Subbarao Malireddi
- & Thirumala-Devi Kanneganti
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Article
| Open AccessOsteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation
Osteoarthritis (OA) is associated with cartilage disruption, but the underlying mechanisms remain unclear. Here, the authors show that expression of osteoclast-associated receptor (OSCAR) is associated with OA, that its genetic ablation or targeting with OSCAR-Fc fusion protein ameliorates OA in mice by decreasing chondrocyte apoptosis.
- Doo Ri Park
- , Jihee Kim
- & Soo Young Lee
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Article
| Open AccessIdentification of osteogenic progenitor cell-targeted peptides that augment bone formation
Activation of osteogenic cells is essential for bone regeneration. Here, the authors screen a peptide library and identify 2 compounds that promote osteogenic progenitor cell differentiation in vitro, and show that they increase bone formation and fracture repair in mice.
- Min Jiang
- , Ruiwu Liu
- & Wei Yao
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Article
| Open AccessSingle-cell transcriptional networks in differentiating preadipocytes suggest drivers associated with tissue heterogeneity
The origin of the heterogeneity of metabolic and inflammatory profiles exhibited by white adipocytes is little understood. Here, using scRNA-seq and computational methods, the authors show that differentiating preadipocytes exhibit gene expression differences and suggest underlying regulators.
- Alfred K. Ramirez
- , Simon N. Dankel
- & Simon Kasif
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Article
| Open AccessFGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis
Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.
- Farnaz Shamsi
- , Ruidan Xue
- & Yu-Hua Tseng
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Article
| Open AccessEnvironmental arginine controls multinuclear giant cell metabolism and formation
Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.
- Julia S. Brunner
- , Loan Vulliard
- & Gernot Schabbauer
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Article
| Open AccessMacrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M
Fibrosis is a hallmark of several cardiac pathologies and its underlying mechanisms are still poorly defined. Here the authors show that macrophage hypoxia signaling following transverse aortic constriction in mice suppresses the activation of cardiac fibroblasts by secreting oncostatin M.
- Hajime Abe
- , Norihiko Takeda
- & Issei Komuro
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Article
| Open AccessImmunoregulation of macrophages by dynamic ligand presentation via ligand–cation coordination
Control of macrophage adhesion and phenotype is important to biomaterial applications. Here, the authors report on the use of bisphosphonate coated gold nanoparticles by magnesium coordination for the controlled adhesion and polarisation of macrophages in vitro and in vivo and controlled cell release.
- Heemin Kang
- , Boguang Yang
- & Liming Bian
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Article
| Open AccessExcessive mechanical loading promotes osteoarthritis through the gremlin-1–NF-κB pathway
Excessive mechanical stress promotes the development of osteoarthritis. Here Chang et al. identify gremlin-1 as a factor expressed in chondrocytes in response to mechanical stress, and contributing to osteoarthritis via activation of the NF-κB pathway.
- Song Ho Chang
- , Daisuke Mori
- & Taku Saito
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Article
| Open AccessZEB1 protects skeletal muscle from damage and is required for its regeneration
Following muscle damage, an inflammatory response is associated to activation of satellite cells, which drive muscle repair. Here, the authors show that upregulation of Zeb1 in macrophages and muscle fibres regulates inflammation, and also show a role for Zeb1 in maintenance of satellite cell quiescence.
- Laura Siles
- , Chiara Ninfali
- & Antonio Postigo
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Article
| Open AccessSingle-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds
The diversity of fibroblasts contributing to wound healing is unclear. Here, the authors use single-cell RNA-sequencing to identify heterogeneity among murine fibroblasts in the wound and find that recruited myeloid cells contribute to adipocyte regeneration during healing.
- Christian F. Guerrero-Juarez
- , Priya H. Dedhia
- & Maksim V. Plikus
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Article
| Open AccessBMP9 stimulates joint regeneration at digit amputation wounds in mice
Mammalian joints have poor regenerative capacity following amputation. Here, the authors show that in mice, stimulation of the amputation wound with BMP2 and BMP9 stimulates regeneration of a synovial joint that includes bone, cartilage and a synovial cavity.
- Ling Yu
- , Lindsay A. Dawson
- & Ken Muneoka
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Article
| Open AccessHematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis
Osteoarthritis (OA) is associated with cartilage degeneration, and no effective therapy exists. Here, the authors show that the HPIP protein modulates OA progression by regulating Wnt signaling, and that its knockdown in joints via AAV-mediated gene silencing attentuates pathology.
- Quanbo Ji
- , Xiaojie Xu
- & Yan Wang
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Article
| Open AccessRNA-binding protein ZFP36L1 regulates osteoarthritis by modulating members of the heat shock protein 70 family
Osteoarthritis is characterised by degeneration of joint cartilage. Here the authors show that the RNA-binding protein ZFP36L1 is upregulated in chondrocytes of humans and mice with osteoarthritis, and that its knockdown in mouse joints protects chondrocytes against apoptosis by modulating the function of heat shock proteins.
- Young-Ok Son
- , Hyo-Eun Kim
- & Jang-Soo Chun
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Article
| Open AccessMale germ cells support long-term propagation of Zika virus
Zika virus (ZIKV) can persist for months in semen and sperm. Here, the authors show that germ cells, compared to other cell types in the reproductive tract, are most susceptible to ZIKV and produce high levels of progeny virus, which coincides with decreased expression of the interferon-stimulated gene Ifi44l.
- Christopher L. Robinson
- , Angie C. N. Chong
- & Shuibing Chen
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Article
| Open AccessProfiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity
Epithelial subpopulations are present in the human breast but how these differentiate or form is unclear. Here, the authors use single-cell RNA sequencing of primary human breast epithelial cells to define previously undescribed luminal, basal epithelial subpopulations and ZEB1-positive basal cells.
- Quy H. Nguyen
- , Nicholas Pervolarakis
- & Kai Kessenbrock
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Article
| Open AccessLsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells
Satellite cells can differentiate both into myocytes and brown adipocytes. Here, the authors show that the histone demethylase Lsd1 prevents adipogenic differentiation of satellite cells by repressing expression of Glis1, and that its ablation changes satellite cell fate towards brown adipocytes and delays muscle regeneration in mice.
- Milica Tosic
- , Anita Allen
- & Roland Schüle
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Article
| Open AccessDirect cell–cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo
Communication between osteoblasts and osteoclasts is essential for bone homeostasis, but the mode of interaction is unclear. The authors use intravital two-photon microscopy in mice to show that these cells directly interact, regulating activity of osteoclasts, and that the interaction is modulated by parathyroid hormone administration.
- Masayuki Furuya
- , Junichi Kikuta
- & Masaru Ishii
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Article
| Open AccessShort-chain fatty acids regulate systemic bone mass and protect from pathological bone loss
Short-chain fatty acids (SCFA) are a main class of metabolites derived from fermentation of dietary fibre in the intestine. Here, the authors show that dietary administration of SCFA is associated with inhibition of osteoclast differentiation, increased bone mass, and reduced pathological bone loss in mice.
- Sébastien Lucas
- , Yasunori Omata
- & Mario M. Zaiss
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Article
| Open AccessDJ-1 controls bone homeostasis through the regulation of osteoclast differentiation
Osteoclasts are involved in arthritis, and their differentiation depends on RANKL signaling. The author show that the ROS-scavenging protein DJ-1 negatively regulates RANKL signaling and that its ablation increases osteoclast numbers and exacerbates bone damage in mouse models of arthritis.
- Hyuk Soon Kim
- , Seung Taek Nam
- & Wahn Soo Choi
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Article
| Open AccessMyoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle
Exon skipping is a strategy for the treatment of Duchenne muscular dystrophy, but has variable efficacy. Here, the authors show that dystrophin restoration occurs preferentially in areas of myofiber regeneration, where antisense oligonucleotides are stored in macrophages and delivered to myoblasts and newly formed myotubes
- James S. Novak
- , Marshall W. Hogarth
- & Terence A. Partridge
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Article
| Open AccessMacrophage-released ADAMTS1 promotes muscle stem cell activation
Satellite cells are crucial for growth and regeneration of skeletal muscle. Here the authors show that in response to muscle injury, macrophages secrete Adamts1, which induces satellite cell activation by modulating Notch1 signaling.
- Hongqing Du
- , Chung-Hsuan Shih
- & Brian J. Feldman
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Article
| Open AccessCD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors
Adipose tissue contains macrophages that can influence both local and systemic metabolism via the secretion of cytokines. Here, Nawaz et al. report that M2-like macrophages, present in adipose tissue, create a microenvironment that inhibits proliferation of adipocyte progenitors due to the secretion of TGF-β1
- Allah Nawaz
- , Aminuddin Aminuddin
- & Kazuyuki Tobe
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Article
| Open AccessSuccinate and its G-protein-coupled receptor stimulates osteoclastogenesis
Bone loss is common in patients with diabetes, but the underlying molecular and cellular mechanisms are unclear. Here the authors show high succinate levels in mice with type 2 diabetes and that succinate can signal through succinate receptor 1 on osteoclasts to induce bone resorption.
- Yuqi Guo
- , Chengzhi Xie
- & Xin Li
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Article
| Open AccessHepcidin inhibits Smad3 phosphorylation in hepatic stellate cells by impeding ferroportin-mediated regulation of Akt
The peptide hormone hepcidin is released from hepatocytes and regulates iron homoeostasis. Here, the authors show that hepcidin also regulates the activation of hepatic stellate cells (HSCs) in mouse models of liver fibrosis by reducing ferroportin expression and inhibiting the HSC response to TGFβ.
- Chang Yeob Han
- , Ja Hyun Koo
- & Sang Geon Kim
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Article
| Open AccessBiphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes
Rela is a transcription factor shown to have seemingly contradictory roles in anabolism and catabolism of cartilage. Here the authors find that Rela prevents chondrocyte apoptosis and that homozygous knockout causes accelerated osteoarthritis in adults, whereas heterozygous knockout suppresses osteoarthritis by maintaining wild-type effects on apoptosis but inhibiting catabolic gene expression.
- Hiroshi Kobayashi
- , Song Ho Chang
- & Taku Saito
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Article
| Open AccessLkb1 controls brown adipose tissue growth and thermogenesis by regulating the intracellular localization of CRTC3
The kinase Lkb1 is expressed in various metabolic tissues and is known to regulate cellular and systemic energy homeostasis. Here, the authors delete Lkb1 specifically in mature adipocytes of mice to show that Lkb1 regulates brown adipose tissue expansion and expression of UCP1.
- Tizhong Shan
- , Yan Xiong
- & Shihuan Kuang
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Article
| Open AccessDazl is a target RNA suppressed by mammalian NANOS2 in sexually differentiating male germ cells
The Nanos family protein, NANOS2, is required for sexual differentiation of male germ cells in mice, however, the molecular RNA targets are unknown. Here, Kato et al. identify Dazl, a germ cell-specific gene, as being a target of NANOS, with stabilized DazlmRNA causing abnormal resumption of the cell cycle.
- Yuzuru Kato
- , Takeo Katsuki
- & Yumiko Saga
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Article
| Open AccessSENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression
Pro-inflammatory NF-κB signalling is regulated by protein sumoylation. Here the authors show that lack of the desumoylating protease SENP1 in fat tissue induces NF-κB activity and inflammation in peri-pancreatic adipocytes, leading to symptoms of type 1 diabetes in mice.
- Lan Shao
- , Huanjiao Jenny Zhou
- & Wang Min
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Article
| Open AccessDNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint
Damage to maternal DNA during meosis can lead to birth defects, abortion or infertility. Here, the authors show that the spindle assembly checkpoint can respond to DNA damage in oocytes by blocking anaphase promoting complex activity and arresting oocytes in meiosis I.
- Josie K. Collins
- , Simon I. R. Lane
- & Keith T. Jones
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Article
| Open AccessCRL4–DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation
The E3 ubiquitin ligase CRL4 regulates oocyte survival through hydroxymethylation of genomic DNA. Here Yuet al. show that CRL4 is also required for oocytes to complete meiosis I by mediating the poly-ubiquitination and proteasomal degradation of the cell cycle regulator protein phosphatase 2A-A subunit.
- Chao Yu
- , Shu-Yan Ji
- & Heng-Yu Fan
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Article
| Open AccessRegion-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues
Bone marrow contains adipocytes, which have been thought to form one type of marrow adipose tissue (MAT). Here, the authors identify two MAT subpopulations in mice and humans—‘regulated’ and ‘constitute’ MAT—which show distinct phenotypic and cellular traits, and respond differently to cold exposure.
- Erica L. Scheller
- , Casey R. Doucette
- & Ormond A. MacDougald
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Article
| Open AccessSelective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements
Insulin resistance in adipose tissue is a hallmark of obesity. Here, the authors generate inducible adipocyte-specific PTEN knockout mice to demonstrate that enhanced insulin sensitivity in adipose tissue is directly linked to improved systemic metabolic homeostasis, despite an increase in fat mass.
- Thomas S. Morley
- , Jonathan Y. Xia
- & Philipp E. Scherer
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Article
| Open AccessDrosophila germ granules are structured and contain homotypic mRNA clusters
What regulates mRNAs transcript localization in the germ granules in Drosophila is unclear. Here Trcek et al.identify that germ plasm proteins are homogeneously distributed in germ granules but once localized, individual mRNAs form homotypic clusters, contributing structure to the germ granules.
- Tatjana Trcek
- , Markus Grosch
- & Ruth Lehmann