Abstract:
:Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Liu Y,Mi Y,Mueller T,Kreibich S,Williams EG,Van Drogen A,Borel C,Frank M,Germain PL,Bludau I,Mehnert M,Seifert M,Emmenlauer M,Sorg I,Bezrukov F,Bena FS,Zhou H,Dehio C,Testa G,Saez-Rodriguez J,Antonarakis SE,Harddoi
10.1038/s41587-019-0037-ysubject
Has Abstractpub_date
2019-03-01 00:00:00pages
314-322issue
3eissn
1087-0156issn
1546-1696pii
10.1038/s41587-019-0037-yjournal_volume
37pub_type
杂志文章abstract::Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implant...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1393
更新日期:2008-04-01 00:00:00
abstract::Linear, medium-chain (C8-C12) hydrocarbons are important components of fuels as well as commodity and specialty chemicals. As industrial microbes do not contain pathways to produce medium-chain chemicals, approaches such as overexpression of endogenous enzymes or deletion of competing pathways are not available to the...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.4022
更新日期:2017-12-01 00:00:00
abstract::We show that selection of drug-resistant bacterial mutants allows the discovery of antibacterial compounds. Mutant strains of a soil-isolated Streptomyces species that does not produce antibacterials synthesize a previously unknown class of antibacterial, which we name piperidamycin. Overall, 6% of non-Streptomyces ac...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1538
更新日期:2009-05-01 00:00:00
abstract::Glycoprotein hormones are noncovalent heterodimers comprised of a common alpha subunit and a hormone-specific beta subunit. Secretion and biologic action of these hormones are dependent on the formation of the heterodimer. The human LH beta subunit is unique among the other beta subunits in that it assembles inefficie...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0797-663
更新日期:1997-07-01 00:00:00
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/s41587-019-0167-2
更新日期:2019-07-01 00:00:00
abstract::Cellular function is critically regulated through degradation of substrates by the proteasome. To enable direct analysis of naturally cleaved proteasomal peptides under physiological conditions, we developed mass spectrometry analysis of proteolytic peptides (MAPP), a method for proteasomal footprinting that allows fo...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4279
更新日期:2018-10-22 00:00:00
abstract::An approach to the systematic identification and quantification of the proteins contained in the microsomal fraction of cells is described. It consists of three steps: (1) preparation of microsomal fractions from cells or tissues representing different states; (2) covalent tagging of the proteins with isotope-coded af...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1001-946
更新日期:2001-10-01 00:00:00
abstract::We developed a modified flagellar type III secretion apparatus to secrete heterologous polypeptides into the growth medium of Escherichia coli. The secretion was facilitated by fusing the 173-bp untranslated DNA fragment upstream of the gene fliC (encoding flagellin) as well as a transcriptional terminator from fliC, ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1077
更新日期:2005-04-01 00:00:00
abstract::The treatment of asthma and allergic rhinitis using unique, humanized anti-IgE monoclonal antibodies with very particular binding specificities is now supported by the results of multiple phase II and III human clinical studies. The therapeutic efficacy of this approach is attributable to several pharmacological mecha...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/72601
更新日期:2000-02-01 00:00:00
abstract::We describe a novel approach to design a set of primers selective for large groups of genes. This method is based on the distribution frequency of all nucleotide combinations (octa- to decanucleotides), and the combined ability of primer pairs, based on these oligonucleotides, to detect genes. By analyzing 1000 human ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0796-857
更新日期:1996-07-01 00:00:00
abstract::Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in one sample. Here we use peptide-major histocompatibility complex (...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3662
更新日期:2016-10-01 00:00:00
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...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3033
更新日期:2014-11-01 00:00:00
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
更新日期:2019-08-01 00:00:00
abstract::Artificial transcription factors containing designer zinc-finger DNA-binding domains (DBDs) have been used to activate or repress expression of a growing number of endogenous genes. We have combined targeted zinc-finger DBD technology with a dimerizer-regulated gene expression system to permit the small-molecule contr...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0702-729
更新日期:2002-07-01 00:00:00
abstract::Efficiently generating evidence of clinical utility is a major challenge for ensuring clinical adoption of valuable diagnostics. A new approach to reimbursement in the United States offers a balance between evidence and incentives for molecular diagnostic tests. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1110-1157
更新日期:2010-11-01 00:00:00
abstract::Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical pract...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1298
更新日期:2007-04-01 00:00:00
abstract::RNA-interference (RNAi) is a potent mechanism, conserved from plants to humans for specific silencing of genes, which holds promise for functional genomics and gene-targeted therapies. Here we show that bacteria engineered to produce a short hairpin RNA (shRNA) targeting a mammalian gene induce trans-kingdom RNAi in v...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1211
更新日期:2006-06-01 00:00:00
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
更新日期:2020-08-01 00:00:00
abstract::Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumo...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2157
更新日期:2012-03-18 00:00:00
abstract::Embryonic stem (ES) cells are a promising source of cardiomyocytes, but clinical application of ES cells has been hindered by the lack of reliable selective differentiation methods. Differentiation into any lineage is partly dependent on the regulatory mechanisms of normal early development. Although several signals, ...
journal_title:Nature biotechnology
pub_type: 信件
doi:10.1038/nbt1093
更新日期:2005-05-01 00:00:00
abstract::Most microbes in the biosphere remain unculturable. Whole genome shotgun (WGS) sequencing of environmental DNA (metagenomics) can be used to study the genetic and metabolic properties of natural microbial communities. However, in communities of high complexity, metagenomics fails to link specific microbes to specific ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1488
更新日期:2008-09-01 00:00:00
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
更新日期:2010-06-01 00:00:00
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: 杂志文章,已发布勘误
doi:10.1038/s41587-020-0457-8
更新日期:2020-03-01 00:00:00
abstract::St. Louis wants to become a hub of agricultural biotechnology. All it needs is more start-ups and funds. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0408-471
更新日期:2008-04-01 00:00:00
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
更新日期:2003-09-01 00:00:00
abstract::The human transcriptome is marked by extensive alternative mRNA splicing and the expression of many closely related genes, which may be difficult to distinguish using standard microarray techniques. Here we describe a sensitive and specific assay for parallel analysis of mRNA isoforms on a fiber-optic microarray platf...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0402-353
更新日期:2002-04-01 00:00:00
abstract::Nucleotide variants, especially those related to epigenetic functions, provide critical regulatory information beyond simple genomic sequence, and they define cell status in higher organisms. 5-Methylcytosine, which is found in DNA, was until recently the only nucleotide variant studied in terms of epigenetics in euka...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.2398
更新日期:2012-11-01 00:00:00
abstract::Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we presen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3350
更新日期:2015-10-01 00:00:00
abstract::Correct reconstruction of macromolecular structure by cryo-electron microscopy (cryo-EM) relies on accurate determination of the orientation of single-particle images. For small (<100 kDa) DNA-binding proteins, obtaining particle images with sufficiently asymmetric features to correctly guide alignment is challenging....
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-020-0716-8
更新日期:2020-10-19 00:00:00
abstract::Type I polyketide synthase (PKS) genes consist of modules approximately 3-6 kb long, which encode the structures of 2-carbon units in polyketide products. Alteration or replacement of individual PKS modules can lead to the biosynthesis of 'unnatural' natural products but existing techniques for this are time consuming...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1128
更新日期:2005-09-01 00:00:00