Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells.

Abstract:

:Transplantation of pancreatic progenitors or insulin-secreting cells derived from human embryonic stem cells (hESCs) has been proposed as a therapy for diabetes. We describe a seven-stage protocol that efficiently converts hESCs into insulin-producing cells. Stage (S) 7 cells expressed key markers of mature pancreatic beta cells, including MAFA, and displayed glucose-stimulated insulin secretion similar to that of human islets during static incubations in vitro. Additional characterization using single-cell imaging and dynamic glucose stimulation assays revealed similarities but also notable differences between S7 insulin-secreting cells and primary human beta cells. Nevertheless, S7 cells rapidly reversed diabetes in mice within 40 days, roughly four times faster than pancreatic progenitors. Therefore, although S7 cells are not fully equivalent to mature beta cells, their capacity for glucose-responsive insulin secretion and rapid reversal of diabetes in vivo makes them a promising alternative to pancreatic progenitor cells or cadaveric islets for the treatment of diabetes.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Rezania A,Bruin JE,Arora P,Rubin A,Batushansky I,Asadi A,O'Dwyer S,Quiskamp N,Mojibian M,Albrecht T,Yang YH,Johnson JD,Kieffer TJ

doi

10.1038/nbt.3033

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

1121-33

issue

11

eissn

1087-0156

issn

1546-1696

pii

nbt.3033

journal_volume

32

pub_type

杂志文章
  • A model of molecular interactions on short oligonucleotide microarrays.

    abstract::High-density short oligonucleotide microarrays have become a widely used tool for measuring gene expression on a large scale. However, details of the mechanism of binding on microarrays remain unclear. Short oligonucleotide probes currently synthesized on microarrays are often ineffective as a result of limited sequen...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt836

    authors: Zhang L,Miles MF,Aldape KD

    更新日期:2003-07-01 00:00:00

  • Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations.

    abstract::The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or zero labeled target pr...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.1641

    authors: Rissin DM,Kan CW,Campbell TG,Howes SC,Fournier DR,Song L,Piech T,Patel PP,Chang L,Rivnak AJ,Ferrell EP,Randall JD,Provuncher GK,Walt DR,Duffy DC

    更新日期:2010-06-01 00:00:00

  • Inovio.

    abstract::A Pennsylvania company hopes to turn synthetic DNA vaccines into rapid response agents against flu epidemics and cancer. ...

    journal_title:Nature biotechnology

    pub_type: 新闻

    doi:10.1038/nbt0213-98

    authors: Rohn J

    更新日期:2013-02-01 00:00:00

  • Purification of recombinant proteins by fusion with thermally-responsive polypeptides.

    abstract::Elastin-like polypeptides (ELPs) undergo a reversible, inverse phase transition. Below their transition temperature (Tt), ELPs are soluble in water, but when the temperature is raised above Tt, phase transition occurs, leading to aggregation of the polypeptide. We demonstrate a method for purification of soluble fusio...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/15100

    authors: Meyer DE,Chilkoti A

    更新日期:1999-11-01 00:00:00

  • The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

    abstract::The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthe...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.2891

    authors: Galdzicki M,Clancy KP,Oberortner E,Pocock M,Quinn JY,Rodriguez CA,Roehner N,Wilson ML,Adam L,Anderson JC,Bartley BA,Beal J,Chandran D,Chen J,Densmore D,Endy D,Grünberg R,Hallinan J,Hillson NJ,Johnson JD,Kuchinsky

    更新日期:2014-06-01 00:00:00

  • Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases.

    abstract::Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 gene...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.3514

    authors: Chen R,Shi L,Hakenberg J,Naughton B,Sklar P,Zhang J,Zhou H,Tian L,Prakash O,Lemire M,Sleiman P,Cheng WY,Chen W,Shah H,Shen Y,Fromer M,Omberg L,Deardorff MA,Zackai E,Bobe JR,Levin E,Hudson TJ,Groop L,Wang J,

    更新日期:2016-05-01 00:00:00

  • Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing.

    abstract::RNA interference (RNAi) is a powerful method for specifically silencing gene expression in diverse cell types. RNAi is mediated by approximately 21-nucleotide small interfering RNAs (siRNAs), which are produced from larger double-stranded RNAs (dsRNAs) in vivo through the action of Dicer, an RNase III-family enzyme. T...

    journal_title:Nature biotechnology

    pub_type:

    doi:10.1038/nbt792

    authors: Myers JW,Jones JT,Meyer T,Ferrell JE Jr

    更新日期:2003-03-01 00:00:00

  • Increased gibberellin biosynthesis in transgenic trees promotes growth, biomass production and xylem fiber length.

    abstract::In most tree-breeding programs worldwide, increasing the trees' growth rates and stem volumes and shortening their rotation times are important aims. Such trees would yield more biomass per unit area. Here we show that overexpressing a key regulatory gene in the biosynthesis of the plant hormone gibberellin (GA) in hy...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/77355

    authors: Eriksson ME,Israelsson M,Olsson O,Moritz T

    更新日期:2000-07-01 00:00:00

  • The endocrine secretion of human insulin and growth hormone by exocrine glands of the gastrointestinal tract.

    abstract::The exocrine pancreas, liver, and submandibular glands of the rat were used to express and secrete two exogenous, human protein hormones (growth hormone and insulin) into blood at physiological concentrations. Transfection, expression, and secretion were achieved by the in vivo retrograde injection of plasmid DNA into...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt1297-1378

    authors: Goldfine ID,German MS,Tseng HC,Wang J,Bolaffi JL,Chen JW,Olson DC,Rothman SS

    更新日期:1997-12-01 00:00:00

  • Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution.

    abstract::Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6%∼96.7%...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.3208

    authors: Li F,Fan G,Lu C,Xiao G,Zou C,Kohel RJ,Ma Z,Shang H,Ma X,Wu J,Liang X,Huang G,Percy RG,Liu K,Yang W,Chen W,Du X,Shi C,Yuan Y,Ye W,Liu X,Zhang X,Liu W,Wei H,Wei S,Huang G,Zhang X,Zhu S,Zhang H,Sun

    更新日期:2015-05-01 00:00:00

  • Presymptomatic visualization of plant-virus interactions by thermography.

    abstract::Salicylic acid (SA), produced by plants as a signal in defense against pathogens, induces metabolic heating mediated by alternative respiration in flowers of thermogenic plants, and, when exogenously applied, increases leaf temperature in nonthermogenic plants. We have postulated that the latter phenomenon would be de...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/11765

    authors: Chaerle L,Van Caeneghem W,Messens E,Lambers H,Van Montagu M,Van Der Straeten D

    更新日期:1999-08-01 00:00:00

  • Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration.

    abstract::Insertional mutagenesis represents a major hurdle to gene therapy and necessitates sensitive preclinical genotoxicity assays. Cdkn2a-/- mice are susceptible to a broad range of cancer-triggering genetic lesions. We exploited hematopoietic stem cells from these tumor-prone mice to assess the oncogenicity of prototypica...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt1216

    authors: Montini E,Cesana D,Schmidt M,Sanvito F,Ponzoni M,Bartholomae C,Sergi Sergi L,Benedicenti F,Ambrosi A,Di Serio C,Doglioni C,von Kalle C,Naldini L

    更新日期:2006-06-01 00:00:00

  • Author Correction: Plants with genetically encoded autoluminescence.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature biotechnology

    pub_type: 已发布勘误

    doi:10.1038/s41587-020-0578-0

    authors: Mitiouchkina T,Mishin AS,Somermeyer LG,Markina NM,Chepurnyh TV,Guglya EB,Karataeva TA,Palkina KA,Shakhova ES,Fakhranurova LI,Chekova SV,Tsarkova AS,Golubev YV,Negrebetsky VV,Dolgushin SA,Shalaev PV,Shlykov D,Melnik OA,

    更新日期:2020-08-01 00:00:00

  • Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells.

    abstract::We compared bona fide human induced pluripotent stem cells (iPSCs) derived from umbilical cord blood (CB) cells and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSCs and K-iPSCs were distinct in genome-wide DNA methylation ...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.2052

    authors: Kim K,Zhao R,Doi A,Ng K,Unternaehrer J,Cahan P,Huo H,Loh YH,Aryee MJ,Lensch MW,Li H,Collins JJ,Feinberg AP,Daley GQ

    更新日期:2011-11-27 00:00:00

  • De novo assembly of soybean wild relatives for pan-genome analysis of diversity and agronomic traits.

    abstract::Wild relatives of crops are an important source of genetic diversity for agriculture, but their gene repertoire remains largely unexplored. We report the establishment and analysis of a pan-genome of Glycine soja, the wild relative of cultivated soybean Glycine max, by sequencing and de novo assembly of seven phylogen...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.2979

    authors: Li YH,Zhou G,Ma J,Jiang W,Jin LG,Zhang Z,Guo Y,Zhang J,Sui Y,Zheng L,Zhang SS,Zuo Q,Shi XH,Li YF,Zhang WK,Hu Y,Kong G,Hong HL,Tan B,Song J,Liu ZX,Wang Y,Ruan H,Yeung CK,Liu J,Wang H,Zhang LJ,Guan RX

    更新日期:2014-10-01 00:00:00

  • Microarray reality checks in the context of a complex disease.

    abstract::A problem in analyzing microarray-based gene expression data is the separation of genes causally involved in a disease from innocent bystander genes, whose expression levels have been secondarily altered by primary changes elsewhere. To investigate this issue systematically in the context of a class of complex human d...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt965

    authors: Miklos GL,Maleszka R

    更新日期:2004-05-01 00:00:00

  • A diverse family of thermostable cytochrome P450s created by recombination of stabilizing fragments.

    abstract::Thermostable enzymes combine catalytic specificity with the toughness required to withstand industrial reaction conditions. Stabilized enzymes also provide robust starting points for evolutionary improvement of other protein properties. We recently created a library of at least 2,300 new active chimeras of the biotech...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt1333

    authors: Li Y,Drummond DA,Sawayama AM,Snow CD,Bloom JD,Arnold FH

    更新日期:2007-09-01 00:00:00

  • Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.

    abstract::The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts ...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/s41587-019-0197-9

    authors: Bargehr J,Ong LP,Colzani M,Davaapil H,Hofsteen P,Bhandari S,Gambardella L,Le Novère N,Iyer D,Sampaziotis F,Weinberger F,Bertero A,Leonard A,Bernard WG,Martinson A,Figg N,Regnier M,Bennett MR,Murry CE,Sinha S

    更新日期:2019-08-01 00:00:00

  • Directed evolution of a para-nitrobenzyl esterase for aqueous-organic solvents.

    abstract::Through sequential generations of random mutagenesis and screening, we have directed the evolution of an esterase for deprotection of an antibiotic p-nitrobenzyl ester in aqueous-organic solvents. Because rapid screening directly on the desired antibiotic (loracarbef) nucleus p-nitrobenzyl ester was not feasible, the ...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt0496-458

    authors: Moore JC,Arnold FH

    更新日期:1996-04-01 00:00:00

  • Bone marrow-derived stem cells initiate pancreatic regeneration.

    abstract::We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood gluco...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt841

    authors: Hess D,Li L,Martin M,Sakano S,Hill D,Strutt B,Thyssen S,Gray DA,Bhatia M

    更新日期:2003-07-01 00:00:00

  • Tandem fluorescent protein timers for in vivo analysis of protein dynamics.

    abstract::The functional state of a cell is largely determined by the spatiotemporal organization of its proteome. Technologies exist for measuring particular aspects of protein turnover and localization, but comprehensive analysis of protein dynamics across different scales is possible only by combining several methods. Here w...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.2281

    authors: Khmelinskii A,Keller PJ,Bartosik A,Meurer M,Barry JD,Mardin BR,Kaufmann A,Trautmann S,Wachsmuth M,Pereira G,Huber W,Schiebel E,Knop M

    更新日期:2012-06-24 00:00:00

  • Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform.

    abstract::The oncofetal fibronectin (B-FN) isoform is present in vessels of neoplastic tissues during angiogenesis but not in mature vessels. B-FN could therefore provide a target for diagnostic imaging and therapy of cancer. Phage display libraries have been used to isolate human antibody fragments with pan-species recognition...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt1197-1271

    authors: Neri D,Carnemolla B,Nissim A,Leprini A,Querzè G,Balza E,Pini A,Tarli L,Halin C,Neri P,Zardi L,Winter G

    更新日期:1997-11-01 00:00:00

  • Correction of chromosomal point mutations in human cells with bifunctional oligonucleotides.

    abstract::A sequence-specific genomic delivery system for the correction of chromosomal mutations was designed by incorporating two different binding domains into a single-stranded oligonucleotide. A repair domain (RD) contained the native sequence of the target region. A third strand-forming domain (TFD) was designed to form a...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/13684

    authors: Culver KW,Hsieh WT,Huyen Y,Chen V,Liu J,Khripine Y,Khorlin A

    更新日期:1999-10-01 00:00:00

  • Sensitive digital quantification of DNA methylation in clinical samples.

    abstract::Analysis of abnormally methylated genes is increasingly important in basic research and in the development of cancer biomarkers. We have developed methyl-BEAMing technology to enable absolute quantification of the number of methylated molecules in a sample. Individual DNA fragments are amplified and analyzed either by...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.1559

    authors: Li M,Chen WD,Papadopoulos N,Goodman SN,Bjerregaard NC,Laurberg S,Levin B,Juhl H,Arber N,Moinova H,Durkee K,Schmidt K,He Y,Diehl F,Velculescu VE,Zhou S,Diaz LA Jr,Kinzler KW,Markowitz SD,Vogelstein B

    更新日期:2009-09-01 00:00:00

  • Directed differentiation of cholangiocytes from human pluripotent stem cells.

    abstract::Although bile duct disorders are well-recognized causes of liver disease, the molecular and cellular events leading to biliary dysfunction are poorly understood. To enable modeling and drug discovery for biliary disease, we describe a protocol that achieves efficient differentiation of biliary epithelial cells (cholan...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.3294

    authors: Ogawa M,Ogawa S,Bear CE,Ahmadi S,Chin S,Li B,Grompe M,Keller G,Kamath BM,Ghanekar A

    更新日期:2015-08-01 00:00:00

  • Metabolic redesign of vitamin E biosynthesis in plants for tocotrienol production and increased antioxidant content.

    abstract::Tocotrienols are the primary form of vitamin E in seeds of most monocot plants, including cereals such as rice and wheat. As potent antioxidants, tocotrienols contribute to the nutritive value of cereal grains in human and livestock diets. cDNAs encoding homogentisic acid geranylgeranyl transferase (HGGT), which catal...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt853

    authors: Cahoon EB,Hall SE,Ripp KG,Ganzke TS,Hitz WD,Coughlan SJ

    更新日期:2003-09-01 00:00:00

  • The complete genome sequence of the meat-borne lactic acid bacterium Lactobacillus sakei 23K.

    abstract::Lactobacillus sakei is a psychotrophic lactic acid bacterium found naturally on fresh meat and fish. This microorganism is widely used in the manufacture of fermented meats and has biotechnological potential in biopreservation and food safety. We have explored the 1,884,661-base-pair (bp) circular chromosome of strain...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt1160

    authors: Chaillou S,Champomier-Vergès MC,Cornet M,Crutz-Le Coq AM,Dudez AM,Martin V,Beaufils S,Darbon-Rongère E,Bossy R,Loux V,Zagorec M

    更新日期:2005-12-01 00:00:00

  • Excision of selectable marker genes from transgenic plants.

    abstract::Selectable marker genes are required to ensure the efficient genetic modification of crops. Economic incentives and safety concerns have prompted the development of several strategies (site-specific recombination, homologous recombination, transposition, and co-transformation) to eliminate these genes from the genome ...

    journal_title:Nature biotechnology

    pub_type: 杂志文章,评审

    doi:10.1038/nbt0602-575

    authors: Hare PD,Chua NH

    更新日期:2002-06-01 00:00:00

  • Therapeutic siRNA silencing in inflammatory monocytes in mice.

    abstract::Excessive and prolonged activity of inflammatory monocytes is a hallmark of many diseases with an inflammatory component. In such conditions, precise targeting of these cells could be therapeutically beneficial while sparing many essential functions of the innate immune system, thus limiting unwanted effects. Inflamma...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/nbt.1989

    authors: Leuschner F,Dutta P,Gorbatov R,Novobrantseva TI,Donahoe JS,Courties G,Lee KM,Kim JI,Markmann JF,Marinelli B,Panizzi P,Lee WW,Iwamoto Y,Milstein S,Epstein-Barash H,Cantley W,Wong J,Cortez-Retamozo V,Newton A,Love K,

    更新日期:2011-10-09 00:00:00

  • Low probability of chloroplast movement from oilseed rape (Brassica napus) into wild Brassica rapa.

    abstract::Pollen-mediated movement of transgenes from transplastomic oilseed rape (Brassica napus) into wild relatives will be avoided if chloroplasts are maternally transmitted. We assess the probability of chloroplast exchange between conventional oilseed rape and wild Brassica rapa to model the future behavior of transplasto...

    journal_title:Nature biotechnology

    pub_type: 杂志文章

    doi:10.1038/7952

    authors: Scott SE,Wilkinson MJ

    更新日期:1999-04-01 00:00:00