Reprogramming-derived gene cocktail increases cardiomyocyte proliferation for heart regeneration.

Abstract:

:Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regulation of several mitosis-related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3-shRNA (FIJs), induced CMs to re-enter the cell cycle and complete mitosis and cytokinesis in vitro More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction. Collectively, our findings present a cocktail FIJs that may be useful in cardiac regeneration and also provide a practical strategy for probing reprogramming assays for regeneration of other tissues.

journal_name

EMBO Mol Med

journal_title

EMBO molecular medicine

authors

Cheng YY,Yan YT,Lundy DJ,Lo AH,Wang YP,Ruan SC,Lin PJ,Hsieh PC

doi

10.15252/emmm.201606558

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

251-264

issue

2

eissn

1757-4676

issn

1757-4684

pii

emmm.201606558

journal_volume

9

pub_type

杂志文章
  • Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies.

    abstract::Formation of pathogenic antibodies is a major problem in replacement therapies for inherited protein deficiencies. For example, antibodies to coagulation factors ('inhibitors') seriously complicate treatment of haemophilia. While immune tolerance induction (ITI) protocols have been developed, inhibitors against factor...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201302859

    authors: Markusic DM,Hoffman BE,Perrin GQ,Nayak S,Wang X,LoDuca PA,High KA,Herzog RW

    更新日期:2013-11-01 00:00:00

  • Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake.

    abstract::The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in int...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201506030

    authors: Zhang Z,Shen M,Gresch PJ,Ghamari-Langroudi M,Rabchevsky AG,Emeson RB,Stamm S

    更新日期:2016-08-01 00:00:00

  • Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity.

    abstract::Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38γ and p38δ regulate the innate immune response to C. ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708485

    authors: Alsina-Beauchamp D,Escós A,Fajardo P,González-Romero D,Díaz-Mora E,Risco A,Martín-Serrano MA,Del Fresno C,Dominguez-Andrés J,Aparicio N,Zur R,Shpiro N,Brown GD,Ardavín C,Netea MG,Alemany S,Sanz-Ezquerro JJ,Cuenda A

    更新日期:2018-05-01 00:00:00

  • Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.

    abstract::High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to ac...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201910681

    authors: Germann M,Zangger N,Sauvain MO,Sempoux C,Bowler AD,Wirapati P,Kandalaft LE,Delorenzi M,Tejpar S,Coukos G,Radtke F

    更新日期:2020-01-09 00:00:00

  • Dissecting human antibody responses: useful, basic and surprising findings.

    abstract::Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target-agnostic approach based...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201808879

    authors: Lanzavecchia A

    更新日期:2018-03-01 00:00:00

  • Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?

    abstract::Mitochondrial diseases can arise from mutations either in mitochondrial DNA or in nuclear DNA encoding mitochondrially destined proteins. Currently, there is no cure for these diseases although treatments to ameliorate a subset of the symptoms are being developed. In this issue of EMBO Molecular Medicine, Khan et al (...

    journal_title:EMBO molecular medicine

    pub_type: 评论,杂志文章

    doi:10.15252/emmm.201404179

    authors: Lightowlers RN,Chrzanowska-Lightowlers ZM

    更新日期:2014-06-01 00:00:00

  • Vaccines for the 21st century.

    abstract::In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2-3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1002/emmm.201403876

    authors: Delany I,Rappuoli R,De Gregorio E

    更新日期:2014-06-01 00:00:00

  • Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function.

    abstract::Mutations of the mitochondrial PTEN (phosphatase and tensin homologue)-induced kinase1 (PINK1) are important causes of recessive Parkinson disease (PD). Studies on loss of function and overexpression implicate PINK1 in apoptosis, abnormal mitochondrial morphology, impaired dopamine release and motor deficits. However,...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.200900006

    authors: Morais VA,Verstreken P,Roethig A,Smet J,Snellinx A,Vanbrabant M,Haddad D,Frezza C,Mandemakers W,Vogt-Weisenhorn D,Van Coster R,Wurst W,Scorrano L,De Strooper B

    更新日期:2009-05-01 00:00:00

  • Macrophage deficiency of miR-21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis.

    abstract::Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. He...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201607492

    authors: Canfrán-Duque A,Rotllan N,Zhang X,Fernández-Fuertes M,Ramírez-Hidalgo C,Araldi E,Daimiel L,Busto R,Fernández-Hernando C,Suárez Y

    更新日期:2017-09-01 00:00:00

  • RGS5 promotes arterial growth during arteriogenesis.

    abstract::Arteriogenesis-the growth of collateral arterioles-partially compensates for the progressive occlusion of large conductance arteries as it may occur as a consequence of coronary, cerebral or peripheral artery disease. Despite being clinically highly relevant, mechanisms driving this process remain elusive. In this con...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201403864

    authors: Arnold C,Feldner A,Pfisterer L,Hödebeck M,Troidl K,Genové G,Wieland T,Hecker M,Korff T

    更新日期:2014-08-01 00:00:00

  • Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.

    abstract::Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combi...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201607284

    authors: Benedetti S,Uno N,Hoshiya H,Ragazzi M,Ferrari G,Kazuki Y,Moyle LA,Tonlorenzi R,Lombardo A,Chaouch S,Mouly V,Moore M,Popplewell L,Kazuki K,Katoh M,Naldini L,Dickson G,Messina G,Oshimura M,Cossu G,Tedesco FS

    更新日期:2018-02-01 00:00:00

  • Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture.

    abstract::Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area com...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201506151

    authors: Maruyama S,Nakamura K,Papanicolaou KN,Sano S,Shimizu I,Asaumi Y,van den Hoff MJ,Ouchi N,Recchia FA,Walsh K

    更新日期:2016-08-01 00:00:00

  • A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis.

    abstract::5'AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201302734

    authors: Zadra G,Photopoulos C,Tyekucheva S,Heidari P,Weng QP,Fedele G,Liu H,Scaglia N,Priolo C,Sicinska E,Mahmood U,Signoretti S,Birnberg N,Loda M

    更新日期:2014-04-01 00:00:00

  • Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation.

    abstract::Growing evidence supports that LKB1-deficient KRAS-driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the KrasLSL-G12D/+ ; Lkb1flox/flox (KL) model show strong plasticity, which...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.202012627

    authors: Tong X,Chen Y,Zhu X,Ye Y,Xue Y,Wang R,Gao Y,Zhang W,Gao W,Xiao L,Chen H,Zhang P,Ji H

    更新日期:2021-01-13 00:00:00

  • A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain.

    abstract::Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911248

    authors: Christensen NR,De Luca M,Lever MB,Richner M,Hansen AB,Noes-Holt G,Jensen KL,Rathje M,Jensen DB,Erlendsson S,Bartling CR,Ammendrup-Johnsen I,Pedersen SE,Schönauer M,Nissen KB,Midtgaard SR,Teilum K,Arleth L,Sørensen AT

    更新日期:2020-06-08 00:00:00

  • Intracellular adenosine regulates epigenetic programming in endothelial cells to promote angiogenesis.

    abstract::The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine-metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201607066

    authors: Xu Y,Wang Y,Yan S,Zhou Y,Yang Q,Pan Y,Zeng X,An X,Liu Z,Wang L,Xu J,Cao Y,Fulton DJ,Weintraub NL,Bagi Z,Hoda MN,Wang X,Li Q,Hong M,Jiang X,Boison D,Weber C,Wu C,Huo Y

    更新日期:2017-09-01 00:00:00

  • A CAG repeat polymorphism of KCNN3 predicts SK3 channel function and cognitive performance in schizophrenia.

    abstract::KCNN3, encoding the small conductance calcium-activated potassium channel SK3, harbours a polymorphic CAG repeat in the amino-terminal coding region with yet unproven function. Hypothesizing that KCNN3 genotypes do not influence susceptibility to schizophrenia but modify its phenotype, we explored their contribution t...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201100135

    authors: Grube S,Gerchen MF,Adamcio B,Pardo LA,Martin S,Malzahn D,Papiol S,Begemann M,Ribbe K,Friedrichs H,Radyushkin KA,Müller M,Benseler F,Riggert J,Falkai P,Bickeböller H,Nave KA,Brose N,Stühmer W,Ehrenreich H

    更新日期:2011-06-01 00:00:00

  • Intellectual disability and nutrition-related health.

    abstract::Intellectual disability (ID) is a condition that affects approximately 1% of the population (Maulik et al, 2011). The numbers may differ across nations, owing to different systems and diagnosis entries or lack of such, but usually range between 0.6 and 3% (Stromme & Valvatne, 1998). Persons with ID are a heterogeneous...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.202012899

    authors: Kolset SO

    更新日期:2020-10-07 00:00:00

  • Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer.

    abstract::Resistance to tamoxifen is a clinically major challenge in breast cancer treatment. Although downregulation of estrogen receptor-alpha (ERα) is the dominant mechanism of tamoxifen resistance, the reason for ERα decrease during tamoxifen therapy remains elusive. Herein, we reported that Spalt-like transcription factor ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201910638

    authors: Ye L,Lin C,Wang X,Li Q,Li Y,Wang M,Zhao Z,Wu X,Shi D,Xiao Y,Ren L,Jian Y,Yang M,Ou R,Deng G,Ouyang Y,Chen X,Li J,Song L

    更新日期:2019-12-01 00:00:00

  • TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance.

    abstract::Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease (AD). Antibodies against amyloid β-peptide (Aβ) bind to amyloid plaques and induce their clearance by microglia via Fc receptor-mediated phagocytosis. Dysfunctions of microglia may play a pivotal role in AD pathogenesis and...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201606370

    authors: Xiang X,Werner G,Bohrmann B,Liesz A,Mazaheri F,Capell A,Feederle R,Knuesel I,Kleinberger G,Haass C

    更新日期:2016-09-01 00:00:00

  • Hacking cell differentiation: transcriptional rerouting in reprogramming, lineage infidelity and metaplasia.

    abstract::Initiating neoplastic cell transformation events are of paramount importance for the comprehension of regeneration and vanguard oncogenic processes but are difficult to characterize and frequently clinically overlooked. In epithelia, pre-neoplastic transformation stages are often distinguished by the appearance of phe...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1002/emmm.201302834

    authors: Regalo G,Leutz A

    更新日期:2013-08-01 00:00:00

  • V600EBraf induces gastrointestinal crypt senescence and promotes tumour progression through enhanced CpG methylation of p16INK4a.

    abstract::The majority of human colorectal cancers (CRCs) are initiated by mutations arising in the adenomatous polyposis coli (APC) tumour suppressor gene. However, a new class of non-APC mutated CRCs has been defined that have a serrated histopathology and carry the (V600E)BRAF oncogene. Here we have investigated the pathogen...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201000099

    authors: Carragher LA,Snell KR,Giblett SM,Aldridge VS,Patel B,Cook SJ,Winton DJ,Marais R,Pritchard CA

    更新日期:2010-11-01 00:00:00

  • Identification of the HSPB4/TLR2/NF-κB axis in macrophage as a therapeutic target for sterile inflammation of the cornea.

    abstract::Sterile inflammation underlies many diseases of the cornea including serious chemical burns and the common dry eye syndrome. In search for therapeutic targets for corneal inflammation, we defined the kinetics of neutrophil infiltration in a model of sterile injury to the cornea and identified molecular and cellular me...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201200221

    authors: Oh JY,Choi H,Lee RH,Roddy GW,Ylöstalo JH,Wawrousek E,Prockop DJ

    更新日期:2012-05-01 00:00:00

  • Chimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses.

    abstract::Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adul...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708078

    authors: Olmedillas E,Cano O,Martínez I,Luque D,Terrón MC,McLellan JS,Melero JA,Más V

    更新日期:2018-02-01 00:00:00

  • A KDM6A-KLF10 reinforcing feedback mechanism aggravates diabetic podocyte dysfunction.

    abstract::Diabetic nephropathy is the leading cause of end-stage renal disease. Although dysfunction of podocytes, also termed glomerular visceral epithelial cells, is critically associated with diabetic nephropathy, the mechanism underlying podocyte dysfunction still remains obscure. Here, we identify that KDM6A, a histone lys...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201809828

    authors: Lin CL,Hsu YC,Huang YT,Shih YH,Wang CJ,Chiang WC,Chang PJ

    更新日期:2019-05-01 00:00:00

  • Making the most of what you've got: optimizing residual OXPHOS function in mitochondrial diseases.

    abstract::Patients affected by mitochondrial OXPHOS disorders are still faced with a grim lack of therapeutic options. In this Closeup, Carlos Moraes revisits the recent data by Giovanni Manfredi on PKA's functions in the mitochondria and now its modulation can improve respiration and ATP production in COX-defective cells. ...

    journal_title:EMBO molecular medicine

    pub_type: 评论,杂志文章

    doi:10.1002/emmm.200900049

    authors: Moraes CT

    更新日期:2009-11-01 00:00:00

  • Non-invasive prognostic protein biomarker signatures associated with colorectal cancer.

    abstract::The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with c...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201404874

    authors: Surinova S,Radová L,Choi M,Srovnal J,Brenner H,Vitek O,Hajdúch M,Aebersold R

    更新日期:2015-09-01 00:00:00

  • Molecular pathogenesis of spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins.

    abstract::The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mut...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201303809

    authors: Bin BH,Hojyo S,Hosaka T,Bhin J,Kano H,Miyai T,Ikeda M,Kimura-Someya T,Shirouzu M,Cho EG,Fukue K,Kambe T,Ohashi W,Kim KH,Seo J,Choi DH,Nam YJ,Hwang D,Fukunaka A,Fujitani Y,Yokoyama S,Superti-Furga A,Ikegawa S,

    更新日期:2014-08-01 00:00:00

  • Metronomic chemotherapy offsets HIFα induction upon maximum-tolerated dose in metastatic cancers.

    abstract::Conventional maximum-tolerated dose (MTD) chemotherapy relies on periodic, massive cancer cell ablation events followed by treatment-free intermissions, stereotypically resulting in resistance, relapse, and mortality. Furthermore, MTD chemotherapy can promote metastatic dissemination via activation of a transcriptiona...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911416

    authors: Schito L,Rey S,Xu P,Man S,Cruz-Muñoz W,Kerbel RS

    更新日期:2020-09-07 00:00:00

  • An IgG-based bispecific antibody for improved dual targeting in PSMA-positive cancer.

    abstract::The prostate-specific membrane antigen (PSMA) has been demonstrated in numerous studies to be expressed specifically on prostate carcinoma cells and on the neovasculature of several other cancer entities. However, the simultaneous expression of PSMA on both, tumor cells as well as tumor vessels remains unclear, even i...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911902

    authors: Zekri L,Vogt F,Osburg L,Müller S,Kauer J,Manz T,Pflügler M,Maurer A,Heitmann JS,Hagelstein I,Märklin M,Hörner S,Todenhöfer T,Calaminus C,Stenzl A,Pichler B,la Fougère C,Schneider MA,Rammensee HG,Zender L,Sipos B,

    更新日期:2020-12-29 00:00:00