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| Open AccessZBTB20 is required for anterior pituitary development and lactotrope specification
The pituitary is a complex structure with the anterior lobe containing five specialized cell types secreting different hormones. Here Cao et al. unravel a role for ZBTB20 in pituitary development and specifically in lactrotrope specification.
- Dongmei Cao
- , Xianhua Ma
- & Weiping J. Zhang
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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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| Open AccessEssential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation
The role of TFIID core module TAFs (TATA-binding protein-associated factors) in embryogenesis is unknown. Here, the authors show that Taf4 is essential at mid-gestation and for complete neuronal differentiation of embryonic stem cells, but that Taf4a and Taf4b are redundant at early embryonic stages.
- Diana Langer
- , Igor Martianov
- & Irwin Davidson
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| Open AccessCiliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation
Primary cilia are highly conserved microtubule-based organelles that play essential roles in several cellular processes including osteogenesis. Here the authors show that intraflagellar protein IFT80 regulates osteoblast differentiation by balancing signalling though the canonical and non-canonical Hedgehog pathways.
- Xue Yuan
- , Jay Cao
- & Shuying Yang
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Article
| Open AccessNuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation
The transcription factor, serum response factor, SRF regulates critical smooth muscle (SM) contractile gene expression but what else controls SM differentiation is unclear. Here, Horita et al. demonstrate that nuclear PTEN acts with SRF at the transcriptional level to maintain the differentiated SM phenotype.
- Henrick Horita
- , Christina L. Wysoczynski
- & Mary C. M. Weiser-Evans
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| Open AccessNon-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells
The methylation of non-CpG residues is a poorly understood marker of pluripotent cells, gradually lost as cells differentiate. Here the authors show non-CG methylation can be used as a marker of differentiation potential.
- Lee M. Butcher
- , Mitsuteru Ito
- & Stephan Beck
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| Open AccessGenetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
There has been limited success in generating tissues from human induced pluripotent stem cells (hiPSCs). Here, the authors genetically engineer expression of the transcription factor Gata6 in a single isogenic hiPSC population resulting in complex tissue structures that exhibit liver bud-like properties.
- Patrick Guye
- , Mohammad R. Ebrahimkhani
- & Ron Weiss
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| Open AccessHuman pancreatic beta-like cells converted from fibroblasts
Insulin-producing pancreatic beta cells, generatedin vitro, could lead to new anti-diabetic therapies. Here, Zhu et al. convert human fibroblasts into endodermal progenitors that differentiate in vitrointo glucose-responsive beta-like cells that, following transplantation in mice, protect from diabetes.
- Saiyong Zhu
- , Holger A. Russ
- & Sheng Ding
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Article
| Open AccessMBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response
Fibroblast-to-myofibroblast differentiation is crucial for wound healing and regeneration. Davis et al. describe a new regulatory mechanism underlying myofibroblast differentiation via the RNA-binding protein MBNL1, which promotes the maturation of certain mRNA transcripts that are integral nodes in fibroblast differentiation.
- Jennifer Davis
- , Nathan Salomonis
- & Jeffery D. Molkentin
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| Open AccessAneuploidy causes premature differentiation of neural and intestinal stem cells
It is unclear why certain tissues are more susceptible to the consequences of aneuploidy. Here, in Drosophila, Gogendeau et al.identify aneuploidy as the cause of lengthened G1 and premature differentiation in both neural and adult intestinal stem cells, which prevents cells with abnormal genomes from cycling.
- Delphine Gogendeau
- , Katarzyna Siudeja
- & Renata Basto
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| Open AccessEnhancer repertoires are reshaped independently of early priming and heterochromatin dynamics during B cell differentiation
Enhancers in differentiated haematopoietic cells are generally believed to be primed prior to lineage commitment. Here, the authors show that early priming and Polycomb group mediated silencing have minor roles in shaping the enhancer repertoire in differentiated B cells and that most active enhancers are generated de novo.
- Mohamed-Amin Choukrallah
- , Shuang Song
- & Patrick Matthias
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Article
| Open Access14-3-3ζ coordinates adipogenesis of visceral fat
14-3-3 family proteins are adaptor proteins involved in various cellular functions. Here Lim et al. show that 14-3-3ζ regulates adipogenesis in vitro, and the formation of visceral fat in mice, by reducing autophagic degradation of the adipogenic master transcription factor C/EBP-δ.
- Gareth E. Lim
- , Tobias Albrecht
- & James D. Johnson
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miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3
microRNAs have emerged as important components of numerous gene regulatory networks. Here the authors demonstrate that miR-218 is an essential component of the gene regulatory network that controls motor neuron fate specification in the developing spinal cord.
- Karen P. Thiebes
- , Heejin Nam
- & Soo-Kyung Lee
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| Open AccessA post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status
Nervous system development relies on coherent up-regulation of extensive genes in a precise spatiotemporal manner. Here, the authors show that miR-9/TTP circuitry ensures coordinated up-regulation of neuronal mRNAs in neurons and limits unscheduled accumulation of these transcripts in non-neuronal cells.
- Weijun Dai
- , Wencheng Li
- & Eugene V. Makeyev
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Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
Brg1 is part of the SWI/SNF chromatin remodelling complex that is essential for embryonic development. Here, the authors show that Brg1 is the target of two opposing calcium-regulated molecules involved in myogenesis: calcineurin, which promotes myogenesis, and protein kinase C β (PKCβ), which inhibits it.
- Brian T. Nasipak
- , Teresita Padilla-Benavides
- & Anthony N. Imbalzano
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Article
| Open AccessNkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation
Guidepost cells provide guidance cues that orient growing axons in the brain but little is known about the midline guidepost cells that populate the mouse anterior commissure (AC). Here, the authors show that the transcription factor Nkx2.1 regulates the differentiation of astroglia and neurons that cooperate to guide AC axons through the expression of Slit2.
- Shilpi Minocha
- , Delphine Valloton
- & Cécile Lebrand
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| Open AccessLive-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear
Precise control of stereocilia length by auditory hair cells is vital for normal hearing. Drummond et al. follow in real-time the incorporation of actin into these structures and show that while the actin core is remarkably stable, and actin polymerization is limited to their distal tips.
- Meghan C. Drummond
- , Melanie Barzik
- & Thomas B. Friedman
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The transcription factor Foxc1 is necessary for Ihh–Gli2-regulated endochondral ossification
Skeletal development relies on endochondral ossification. Here the authors show that transcription factors Foxc1 and Gli2 interact to modulate expression of Ihh target genes that control endochondral ossification, and that disruption of this interaction partly underlies skeletal disorders in the Axenfeld–Rieger syndrome.
- Michiko Yoshida
- , Kenji Hata
- & Toshiyuki Yoneda
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| Open AccessEpigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs
Tissue-specific functions have been established for some lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, the authors report tissue-specific epigenomic regulation of 3,753 lincRNAs and their strong connection with tissue-specific pathways.
- Viren Amin
- , R. Alan Harris
- & Aleksandar Milosavljevic
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NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2
N-alpha-acetyltransferase 10 (NAA10) regulates cell growth and proliferation. Here the authors show that NAA10 also has a role in osteogenesis, by fine-tuning the activity of the osteogenic transcription factor Runx2.
- Haejin Yoon
- , Hye-Lim Kim
- & Jong-Wan Park
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Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production
Dendritic cells (DCs) initiate distinct arms of immunity in response to different classes of pathogens. Here Gringhuis et al. show that DCs produce IL-27 upon sensing fucose-containing pathogen ligands via DC-SIGN, promoting follicular T helper cell differentiation and antibody production.
- Sonja I. Gringhuis
- , Tanja M. Kaptein
- & Teunis B. H. Geijtenbeek
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| Open AccessNucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming
Changes in chromatin structure impact gene expression programs by modulating accessibility to the transcription machinery. Here, West et al. explore differences in nucleosome occupancy between mammalian pluripotent and somatic cells and uncover regulatory regions likely to play key roles in determining cell identity.
- Jason A. West
- , April Cook
- & Robert E. Kingston
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IKKα restoration via EZH2 suppression induces nasopharyngeal carcinoma differentiation
Nasopharyngeal carcinomas often present as undifferentiated tumours. Here, Yan et al. show that reduced expression of IKK via promoter methylation results in the undifferentiated phenotype of the tumours and that treatment with retinoic acid can reverse these features.
- Min Yan
- , Yan Zhang
- & Quentin Liu
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| Open AccessLin28a regulates neuronal differentiation and controls miR-9 production
microRNAs regulate gene expression and control cell fate and differentiation processes. In this work, Nowak et al. reveal that brain-specific miR-9 is under post-transcriptional control and that the pre-miR-9 binding protein Lin28a decreases the levels of mature miR-9 during retinoic acid-mediated neuronal differentiation.
- Jakub S. Nowak
- , Nila Roy Choudhury
- & Gracjan Michlewski
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| Open AccessEpigenetic plasticity of Cd8a locus during CD8+ T-cell development and effector differentiation and reprogramming
CD8 expression levels on peripheral CD8+ T cells are regulated during development and effector differentiation. Here, the authors show that methylation patterns at the Cd8a locus, whose product is essential for surface CD8 expression, can change during T-cell development, activation, cytokine polarization and reprogramming.
- Kim L. Harland
- , E. Bridie Day
- & Anne Kelso
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High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1
Motor neurons generated from human pluripotent stem cells are used for disease modelling and drug screening. Here the authors present a protocol for efficient generation of mature spinal motor neurons from human pluripotent stem cells by precisely timing the application of the neural patterning molecule retinoic acid.
- Qiuhao Qu
- , Dong Li
- & Fei Wang
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Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation
Adipocyte differentiation is accompanied by large scale changes in the actin cytoskeleton. Here, Nobusue et al.show that binding to G-actin sequesters the transcriptional coactivator MKL1 in the cytoplasm, and triggers differentiation by inducing the expression of pro-adipogenic transcription factor PPARγ.
- Hiroyuki Nobusue
- , Nobuyuki Onishi
- & Koichiro Kano
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Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation
Asthma is often characterized by Th2-mediated inflammatory responses, which are initiated by lung dendritic cells. Here, Williams et al.demonstrate that dendritic cell expression of transcription factor IRF4 drives Th2 differentiation through IL-33 and IL-10 activation.
- Jesse W. Williams
- , Melissa Y. Tjota
- & Anne I. Sperling
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Early adipogenesis is regulated through USP7-mediated deubiquitination of the histone acetyltransferase TIP60
Tip60 is a transcriptional coregulator that has an important role in differentiation. Here, Gao et al. demonstrate that the deubiquitination of Tip60 by USP7, a dominant deubiquitinating enzyme, is a key mechanism in early adipogenesis regulation.
- Yuan Gao
- , Arjen Koppen
- & Eric Kalkhoven
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The ARNT–STAT3 axis regulates the differentiation of intestinal intraepithelial TCRαβ+CD8αα+ cells
Intraepithelial lymphocytes (IELs) defend against pathogens in the gut, and their differentiation depends on both diet and microbiota-derived factors. Nakajima et al. show that signalling through the aryl hydrocarbon receptor nuclear translocator and STAT3 is required for the development of a subset of IELs.
- Kohei Nakajima
- , Yoichi Maekawa
- & Koji Yasutomo
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Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity
B cells are thought to divide asymmetrically to generate distinct lineages required for adaptive immunity. Hawkins et al. find that surprisingly, mice lacking components of a complex required for asymmetric cell division display normal responses to vaccination and viral infection.
- Edwin D. Hawkins
- , Jane Oliaro
- & Sarah M. Russell
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| Open AccessmiR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit
Brown fat can dissipate energy as heat and has an important role in energy homoeostasis of rodents and possibly humans. Chenet al. show that microRNA 155 regulates the differentiation of brown adipocytes as well as the 'browning' of white fat cells in mice.
- Yong Chen
- , Franziska Siegel
- & Alexander Pfeifer
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Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function
Splicing factors, such as the protein SRSF3, regulate mRNA metabolism but are hard to study in vivobecause genetic kockouts are usually lethal. Here, Sen and colleagues create mice with a hepatocyte-specific knockout of Srsf3 and demonstrate its role in hepatocyte differentiation and liver function.
- Supriya Sen
- , Hassan Jumaa
- & Nicholas J. G. Webster
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| Open AccessUnfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation
The protein OASIS belongs to the CREB/ATF transcription factor family and is involved in endoplasmic reticulum stress responses. Saito and colleagues show that these stress responses temporally activate OASIS in neural precursor cells, resulting in their differentiation into astrocytes.
- Atsushi Saito
- , Soshi Kanemoto
- & Kazunori Imaizumi
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c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling
Osteoblast maturation is regulated by c-Src and IL-6, but how these signalling pathways are integrated is not known. Here c-Src is shown to induce 1GFBP5 in immature osteoblasts in a STAT3 and IL-6-dependent manner, in mature osteoblasts, which express lower levels of c-Src, this signalling is lost.
- Barbara Peruzzi
- , Alfredo Cappariello
- & Anna Teti
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| Open AccessProliferating versus differentiating stem and cancer cells exhibit distinct midbody-release behaviour
During cell division, a cytoplasmic bridge—the midbody—forms between the nascent daughter cells, but it has been unclear under which conditions this is retained by a daughter cell or released. Now, Ettinger and colleagues show that midbody-release occurs more frequently in stem cells compared with cancer cells.
- Andreas W. Ettinger
- , Michaela Wilsch-Bräuninger
- & Wieland B. Huttner
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| Open AccessIdentification of vertebra-like elements and their possible differentiation from sclerotomes in the hagfish
Hagfish, a group of extant jawless fish, lack true vertebrae, but it is not clear if hagfish lack all vertebrata-like structures. Here the authors report the presence of vertebra-like cartilages in the in-shore hagfish, suggesting that the hagfish underwent secondary reduction of vertebra.
- Kinya G. Ota
- , Satoko Fujimoto
- & Shigeru Kuratani