RFX6 regulates insulin secretion by modulating Ca2+ homeostasis in human β cells.

Abstract:

:Development and function of pancreatic β cells involve the regulated activity of specific transcription factors. RFX6 is a transcription factor essential for mouse β cell differentiation that is mutated in monogenic forms of neonatal diabetes. However, the expression and functional roles of RFX6 in human β cells, especially in pathophysiological conditions, are poorly explored. We demonstrate the presence of RFX6 in adult human pancreatic endocrine cells. Using the recently developed human β cell line EndoC-βH2, we show that RFX6 regulates insulin gene transcription, insulin content, and secretion. Knockdown of RFX6 causes downregulation of Ca(2+)-channel genes resulting in the reduction in L-type Ca(2+)-channel activity that leads to suppression of depolarization-evoked insulin exocytosis. We also describe a previously unreported homozygous missense RFX6 mutation (p.V506G) that is associated with neonatal diabetes, which lacks the capacity to activate the insulin promoter and to increase Ca(2+)-channel expression. Our data therefore provide insights for understanding certain forms of neonatal diabetes.

journal_name

Cell Rep

journal_title

Cell reports

authors

Chandra V,Albagli-Curiel O,Hastoy B,Piccand J,Randriamampita C,Vaillant E,Cavé H,Busiah K,Froguel P,Vaxillaire M,Rorsman P,Polak M,Scharfmann R

doi

10.1016/j.celrep.2014.11.010

subject

Has Abstract

pub_date

2014-12-24 00:00:00

pages

2206-18

issue

6

issn

2211-1247

pii

S2211-1247(14)00964-4

journal_volume

9

pub_type

杂志文章
  • miR-17-92 Cluster Regulates Adult Hippocampal Neurogenesis, Anxiety, and Depression.

    abstract::Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here, we show that altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact on ne...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.06.101

    authors: Jin J,Kim SN,Liu X,Zhang H,Zhang C,Seo JS,Kim Y,Sun T

    更新日期:2016-08-09 00:00:00

  • The functional antagonism between Eg5 and dynein in spindle bipolarization is not compatible with a simple push-pull model.

    abstract::During cell division, the molecular motor Eg5 crosslinks overlapping antiparallel microtubules and pushes them apart to separate mitotic spindle poles. Dynein has been proposed as a direct antagonist of Eg5 at the spindle equator, pulling on antiparallel microtubules and favoring spindle collapse. Some of the experime...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2012.03.006

    authors: Florian S,Mayer TU

    更新日期:2012-05-31 00:00:00

  • Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-β Pathway.

    abstract::In glioblastoma, invasion and proliferation are presumed to be mutually exclusive events; however, the molecular mechanisms that mediate this switch at the cellular level remain elusive. Previously, we have shown that phospho-OLIG2, a central-nervous-system-specific transcription factor, is essential for tumor growth ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.06.045

    authors: Singh SK,Fiorelli R,Kupp R,Rajan S,Szeto E,Lo Cascio C,Maire CL,Sun Y,Alberta JA,Eschbacher JM,Ligon KL,Berens ME,Sanai N,Mehta S

    更新日期:2016-07-26 00:00:00

  • Discovery and Characterization of piRNAs in the Human Fetal Ovary.

    abstract::Piwi-interacting RNAs (piRNAs), a class of 26- to 32-nt non-coding RNAs (ncRNAs), function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.09.030

    authors: Williams Z,Morozov P,Mihailovic A,Lin C,Puvvula PK,Juranek S,Rosenwaks Z,Tuschl T

    更新日期:2015-10-27 00:00:00

  • Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis.

    abstract::The Piwi-piRNA pathway is well known for its germline function, yet its somatic role remains elusive. We show here that Piwi is required autonomously not only for germline stem cell (GSC) but also for somatic cyst stem cell (CySC) maintenance in the Drosophila testis. Reducing Piwi activity in the testis caused defect...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.06.004

    authors: Gonzalez J,Qi H,Liu N,Lin H

    更新日期:2015-07-07 00:00:00

  • Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance.

    abstract::Colorectal cancer (CRC) initiation and growth is often attributed to stem cells, yet little is known about the regulation of these cells. We show here that a subpopulation of Prox1-transcription-factor-expressing cells have stem cell activity in intestinal adenomas, but not in the normal intestine. Using in vivo model...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.08.034

    authors: Wiener Z,Högström J,Hyvönen V,Band AM,Kallio P,Holopainen T,Dufva O,Haglund C,Kruuna O,Oliver G,Ben-Neriah Y,Alitalo K

    更新日期:2014-09-25 00:00:00

  • CD57+ Memory T Cells Proliferate In Vivo.

    abstract::A central paradigm in the field of lymphocyte biology asserts that replicatively senescent memory T cells express the carbohydrate epitope CD57. These cells nonetheless accumulate with age and expand numerically in response to persistent antigenic stimulation. Here, we use in vivo deuterium labeling and ex vivo analys...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.108501

    authors: Ahmed R,Miners KL,Lahoz-Beneytez J,Jones RE,Roger L,Baboonian C,Zhang Y,Wang ECY,Hellerstein MK,McCune JM,Baird DM,Price DA,Macallan DC,Asquith B,Ladell K

    更新日期:2020-12-15 00:00:00

  • Roles of H3K27me2 and H3K27me3 Examined during Fate Specification of Embryonic Stem Cells.

    abstract::The polycomb repressive complex 2 (PRC2) methylates lysine 27 of histone H3 (H3K27) through its catalytic subunit Ezh2. PRC2-mediated di- and tri-methylation (H3K27me2/H3K27me3) have been interchangeably associated with gene repression. However, it remains unclear whether these two degrees of H3K27 methylation have di...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.09.087

    authors: Juan AH,Wang S,Ko KD,Zare H,Tsai PF,Feng X,Vivanco KO,Ascoli AM,Gutierrez-Cruz G,Krebs J,Sidoli S,Knight AL,Pedersen RA,Garcia BA,Casellas R,Zou J,Sartorelli V

    更新日期:2016-10-25 00:00:00

  • Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism.

    abstract::Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.02.044

    authors: Mishra D,Richard JE,Maric I,Porteiro B,Häring M,Kooijman S,Musovic S,Eerola K,López-Ferreras L,Peris E,Grycel K,Shevchouk OT,Micallef P,Olofsson CS,Wernstedt Asterholm I,Grill HJ,Nogueiras R,Skibicka KP

    更新日期:2019-03-12 00:00:00

  • Flow Dynamics and HSPC Homing in Bone Marrow Microvessels.

    abstract::Measurements of flow velocities at the level of individual arterial vessels and sinusoidal capillaries are crucial for understanding the dynamics of hematopoietic stem and progenitor cell homing in the bone marrow vasculature. We have developed two complementary intravital two-photon imaging approaches to determine bl...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.01.042

    authors: Bixel MG,Kusumbe AP,Ramasamy SK,Sivaraj KK,Butz S,Vestweber D,Adams RH

    更新日期:2017-02-14 00:00:00

  • Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline.

    abstract::Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of the embryonic CNS. The functional significance, if any, of these different populations is not known. Using dual-color reporter mice to distinguish ventrally and dorsally derived OPs, we show that, ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.03.069

    authors: Crawford AH,Tripathi RB,Richardson WD,Franklin RJM

    更新日期:2016-04-26 00:00:00

  • Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity.

    abstract::The translation initiation repressor 4E-BP2 is deamidated in the brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.11.023

    authors: Kouloulia S,Hallin EI,Simbriger K,Amorim IS,Lach G,Amvrosiadis T,Chalkiadaki K,Kampaite A,Truong VT,Hooshmandi M,Jafarnejad SM,Skehel P,Kursula P,Khoutorsky A,Gkogkas CG

    更新日期:2019-12-10 00:00:00

  • A Chemical Screen Identifies Compounds Capable of Selecting for Haploidy in Mammalian Cells.

    abstract::The recent availability of somatic haploid cell lines has provided a unique tool for genetic studies in mammals. However, the percentage of haploid cells rapidly decreases in these cell lines, which we recently showed is due to their overgrowth by diploid cells present in the cultures. Based on this property, we have ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.06.060

    authors: Olbrich T,Vega-Sendino M,Murga M,de Carcer G,Malumbres M,Ortega S,Ruiz S,Fernandez-Capetillo O

    更新日期:2019-07-16 00:00:00

  • Manipulating Hippocampal Place Cell Activity by Single-Cell Stimulation in Freely Moving Mice.

    abstract::Learning critically depends on the ability to rapidly form and store non-overlapping representations of the external world. In line with their postulated role in episodic memory, hippocampal place cells can undergo a rapid reorganization of their firing fields upon contextual manipulations. To explore the mechanisms u...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.03.031

    authors: Diamantaki M,Coletta S,Nasr K,Zeraati R,Laturnus S,Berens P,Preston-Ferrer P,Burgalossi A

    更新日期:2018-04-03 00:00:00

  • HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification.

    abstract::The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8(+) T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitop...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.03.031

    authors: Tenzer S,Crawford H,Pymm P,Gifford R,Sreenu VB,Weimershaus M,de Oliveira T,Burgevin A,Gerstoft J,Akkad N,Lunn D,Fugger L,Bell J,Schild H,van Endert P,Iversen AKN

    更新日期:2014-04-24 00:00:00

  • Astrocytic l-Lactate Signaling Facilitates Amygdala-Anterior Cingulate Cortex Synchrony and Decision Making in Rats.

    abstract::Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as a key brain region for mediating visceral-pain-cognitive interactions. Recently, we characterized impairments of long-term potentiation and spike-field coherence in the basolateral amygdala (BLA)-ACC network in association with a decision...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.11.012

    authors: Wang J,Tu J,Cao B,Mu L,Yang X,Cong M,Ramkrishnan AS,Chan RHM,Wang L,Li Y

    更新日期:2017-11-28 00:00:00

  • The Zonal Organization of Odorant Receptor Gene Choice in the Main Olfactory Epithelium of the Mouse.

    abstract::A mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) typically expresses one allele of one odorant receptor (OR) gene. It is widely thought that the great majority of the 1,141 intact mouse OR genes are expressed in one of four MOE zones (or bands or stripes), which are largely non-overlappin...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.02.110

    authors: Zapiec B,Mombaerts P

    更新日期:2020-03-24 00:00:00

  • Reprogramming by De-bookmarking the Somatic Transcriptional Program through Targeting of BET Bromodomains.

    abstract::One critical event in reprogramming to pluripotency is erasure of the somatic transcriptional program of starting cells. Here, we present the proof of principle of a strategy for reprogramming to pluripotency facilitated by small molecules that interfere with the somatic transcriptional memory. We show that mild chemi...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.08.060

    authors: Shao Z,Yao C,Khodadadi-Jamayran A,Xu W,Townes TM,Crowley MR,Hu K

    更新日期:2016-09-20 00:00:00

  • DEAD-Box Helicase 18 Counteracts PRC2 to Safeguard Ribosomal DNA in Pluripotency Regulation.

    abstract::Embryonic stem cells (ESCs) exhibit high levels of ribosomal RNA (rRNA) transcription and ribosome biogenesis. Here, we reveal an unexpected role for an essential DEAD-box helicase, DDX18, in antagonizing the polycomb repressive complex 2 (PRC2) to prevent deposition of the repressive H3K27me3 mark onto rDNA in plurip...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.12.021

    authors: Zhang H,Wu Z,Lu JY,Huang B,Zhou H,Xie W,Wang J,Shen X

    更新日期:2020-01-07 00:00:00

  • H3K36 Methylation and the Chromodomain Protein Eaf3 Are Required for Proper Cotranscriptional Spliceosome Assembly.

    abstract::In the eukaryotic cell, spliceosomes assemble onto pre-mRNA cotranscriptionally. Spliceosome assembly takes place in the context of the chromatin environment, suggesting that the state of the chromatin may affect splicing. The molecular details and mechanisms through which chromatin affects splicing, however, are stil...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.05.100

    authors: Leung CS,Douglass SM,Morselli M,Obusan MB,Pavlyukov MS,Pellegrini M,Johnson TL

    更新日期:2019-06-25 00:00:00

  • The architecture of yeast DNA polymerase ζ.

    abstract::DNA polymerase ζ (Polζ) is specialized for the extension step of translesion DNA synthesis (TLS). Despite its central role in maintaining genome integrity, little is known about its overall architecture. Initially identified as a heterodimer of the catalytic subunit Rev3 and the accessory subunit Rev7, yeast Polζ has ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2013.08.046

    authors: Gómez-Llorente Y,Malik R,Jain R,Choudhury JR,Johnson RE,Prakash L,Prakash S,Ubarretxena-Belandia I,Aggarwal AK

    更新日期:2013-10-17 00:00:00

  • AMPK modulates tissue and organismal aging in a non-cell-autonomous manner.

    abstract::AMPK exerts prolongevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that upregulation of AMPK in the adult Drosophila nervous system induces autophagy both in the brain and also in the intestinal epithelium. Induction of autophagy is linked to impr...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.08.006

    authors: Ulgherait M,Rana A,Rera M,Graniel J,Walker DW

    更新日期:2014-09-25 00:00:00

  • XBP1-KLF9 Axis Acts as a Molecular Rheostat to Control the Transition from Adaptive to Cytotoxic Unfolded Protein Response.

    abstract::Transcription factor XBP1s, activated by endoplasmic reticulum (ER) stress in a dose-dependent manner, plays a central role in adaptive unfolded protein response (UPR) via direct activation of multiple genes controlling protein refolding. Here, we report that elevation of ER stress above a critical threshold causes ac...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.09.013

    authors: Fink EE,Moparthy S,Bagati A,Bianchi-Smiraglia A,Lipchick BC,Wolff DW,Roll MV,Wang J,Liu S,Bakin AV,Kandel ES,Lee AH,Nikiforov MA

    更新日期:2018-10-02 00:00:00

  • Drosophila Vision Depends on Carcinine Uptake by an Organic Cation Transporter.

    abstract::Recycling of neurotransmitters is essential for sustained neuronal signaling, yet recycling pathways for various transmitters, including histamine, remain poorly understood. In the first visual ganglion (lamina) of Drosophila, photoreceptor-released histamine is taken up into perisynaptic glia, converted to carcinine,...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.02.009

    authors: Chaturvedi R,Luan Z,Guo P,Li HS

    更新日期:2016-03-08 00:00:00

  • Junctional Adhesion Molecule 2 Represents a Subset of Hematopoietic Stem Cells with Enhanced Potential for T Lymphopoiesis.

    abstract::The distinct lineage potential is a key feature of hematopoietic stem cell (HSC) heterogeneity, but a subset of HSCs specialized for a single lymphoid compartment has not been identified. Here we report that HSCs expressing junctional adhesion molecule 2 (Jam2) at a higher level (Jam2high HSCs) have a greater T cell r...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.05.028

    authors: Radulovic V,van der Garde M,Koide S,Sigurdsson V,Lang S,Kaneko S,Miharada K

    更新日期:2019-06-04 00:00:00

  • Developmental Rewiring between Cerebellar Climbing Fibers and Purkinje Cells Begins with Positive Feedback Synapse Addition.

    abstract::During postnatal development, cerebellar climbing fibers alter their innervation strengths onto supernumerary Purkinje cell targets, generating a one-to-few connectivity pattern in adulthood. To get insight about the processes responsible for this remapping, we reconstructed serial electron microscopy datasets from mi...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.10.081

    authors: Wilson AM,Schalek R,Suissa-Peleg A,Jones TR,Knowles-Barley S,Pfister H,Lichtman JW

    更新日期:2019-11-26 00:00:00

  • Systems-level response to point mutations in a core metabolic enzyme modulates genotype-phenotype relationship.

    abstract::Linking the molecular effects of mutations to fitness is central to understanding evolutionary dynamics. Here, we establish a quantitative relation between the global effect of mutations on the E. coli proteome and bacterial fitness. We created E. coli strains with specific destabilizing mutations in the chromosomal f...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.03.051

    authors: Bershtein S,Choi JM,Bhattacharyya S,Budnik B,Shakhnovich E

    更新日期:2015-04-28 00:00:00

  • Accurate Drug Repositioning through Non-tissue-Specific Core Signatures from Cancer Transcriptomes.

    abstract::Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.09.031

    authors: Xu C,Ai D,Shi D,Suo S,Chen X,Yan Y,Cao Y,Zhang R,Sun N,Chen W,McDermott J,Zhang S,Zeng Y,Han JJ

    更新日期:2018-10-09 00:00:00

  • Paracrine apoptotic effect of p53 mediated by tumor suppressor Par-4.

    abstract::The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apopt...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2013.12.020

    authors: Burikhanov R,Shrestha-Bhattarai T,Hebbar N,Qiu S,Zhao Y,Zambetti GP,Rangnekar VM

    更新日期:2014-01-30 00:00:00

  • Control of embryonic stem cell identity by BRD4-dependent transcriptional elongation of super-enhancer-associated pluripotency genes.

    abstract::Transcription factors and chromatin-remodeling complexes are key determinants of embryonic stem cell (ESC) identity. Here, we demonstrate that BRD4, a member of the bromodomain and extraterminal domain (BET) family of epigenetic readers, regulates the self-renewal ability and pluripotency of ESCs. BRD4 inhibition resu...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.08.055

    authors: Di Micco R,Fontanals-Cirera B,Low V,Ntziachristos P,Yuen SK,Lovell CD,Dolgalev I,Yonekubo Y,Zhang G,Rusinova E,Gerona-Navarro G,Cañamero M,Ohlmeyer M,Aifantis I,Zhou MM,Tsirigos A,Hernando E

    更新日期:2014-10-09 00:00:00