Differentiation-Defective Human Induced Pluripotent Stem Cells Reveal Strengths and Limitations of the Teratoma Assay and In Vitro Pluripotency Assays.

Abstract:

:The ability to form teratomas in vivo containing multiple somatic cell types is regarded as functional evidence of pluripotency for human pluripotent stem cells (hPSCs). Since the Teratoma assay is animal dependent, laborious, and only qualitative, the PluriTest and the hPSC ScoreCard assay have been developed as in vitro alternatives. Here we compared normal hPSCs, induced hPSCs (hiPSCs) with reactivated reprogramming transgenes, and human embryonal carcinoma cells (hECs) in these assays. While normal hPSCs gave rise to typical teratomas, the xenografts of the hECs and the hiPSCs with reactivated reprogramming transgenes were largely undifferentiated and malignant. The hPSC ScoreCard assay confirmed the line-specific differentiation propensities in vitro. However, when undifferentiated cells were analyzed by the PluriTest, only hECs were identified as abnormal whereas all other cell lines were indistinguishable and resembled normal hPSCs. Our results indicate that pluripotency assays are best selected on the basis of intended downstream applications.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Bouma MJ,van Iterson M,Janssen B,Mummery CL,Salvatori DCF,Freund C

doi

10.1016/j.stemcr.2017.03.009

subject

Has Abstract

pub_date

2017-05-09 00:00:00

pages

1340-1353

issue

5

issn

2213-6711

pii

S2213-6711(17)30115-7

journal_volume

8

pub_type

杂志文章
  • The Periostin/Integrin-αv Axis Regulates the Size of Hematopoietic Stem Cell Pool in the Fetal Liver.

    abstract::We earlier showed that outside-in integrin signaling through POSTN-ITGAV interaction plays an important role in regulating adult hematopoietic stem cell (HSC) quiescence. Here, we show that Itgav deletion results in increased frequency of phenotypic HSCs in fetal liver (FL) due to faster proliferation. Systemic deleti...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.06.022

    authors: Biswas A,Roy IM,Babu PC,Manesia J,Schouteden S,Vijayakurup V,Anto RJ,Huelsken J,Lacy-Hulbert A,Verfaillie CM,Khurana S

    更新日期:2020-08-11 00:00:00

  • Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes.

    abstract::When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). Using cell-surface capture proteomics, we i...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2016.07.016

    authors: Mallanna SK,Cayo MA,Twaroski K,Gundry RL,Duncan SA

    更新日期:2016-09-13 00:00:00

  • Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells.

    abstract::Hematopoietic stem cells (HSCs) ensure a life-long regeneration of the blood system and are therefore an important source for transplantation and gene therapy. The teratoma environment supports the complex development of functional HSCs from human pluripotent stem cells, which is difficult to recapitulate in culture. ...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2018.09.010

    authors: Philipp F,Selich A,Rothe M,Hoffmann D,Rittinghausen S,Morgan MA,Klatt D,Glage S,Lienenklaus S,Neuhaus V,Sewald K,Braun A,Schambach A

    更新日期:2018-11-13 00:00:00

  • The epithelial-mesenchymal transition factor SNAIL paradoxically enhances reprogramming.

    abstract::Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) entails a mesenchymal to epithelial transition (MET). While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD) of the epithelial-to-mesenchymal transition (EMT) factor SNAI1 (SNAIL) paradoxically reduce...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2014.09.008

    authors: Unternaehrer JJ,Zhao R,Kim K,Cesana M,Powers JT,Ratanasirintrawoot S,Onder T,Shibue T,Weinberg RA,Daley GQ

    更新日期:2014-11-11 00:00:00

  • LNGFR(+)THY-1(+)VCAM-1(hi+) cells reveal functionally distinct subpopulations in mesenchymal stem cells.

    abstract::Human mesenchymal stem cells (hMSCs), which conventionally are isolated based on their adherence to plastic, are heterogeneous and have poor growth and differentiation, limiting our ability to investigate their intrinsic characteristics. We report an improved prospective clonal isolation technique and reveal that the ...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2013.06.001

    authors: Mabuchi Y,Morikawa S,Harada S,Niibe K,Suzuki S,Renault-Mihara F,Houlihan DD,Akazawa C,Okano H,Matsuzaki Y

    更新日期:2013-07-11 00:00:00

  • Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease.

    abstract::Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP) processing and the accumulation of APP-derived amyloid β (Aβ) peptides are key proces...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2017.02.006

    authors: Brownjohn PW,Smith J,Portelius E,Serneels L,Kvartsberg H,De Strooper B,Blennow K,Zetterberg H,Livesey FJ

    更新日期:2017-04-11 00:00:00

  • Klf2 and Tfcp2l1, Two Wnt/β-Catenin Targets, Act Synergistically to Induce and Maintain Naive Pluripotency.

    abstract::Activation of Wnt/β-catenin signaling can induce both self-renewal and differentiation in naive pluripotent embryonic stem cells (ESCs). To gain insights into the mechanism by which Wnt/β-catenin regulates ESC fate, we screened and characterized its downstream targets. Here, we show that the self-renewal-promoting eff...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2015.07.014

    authors: Qiu D,Ye S,Ruiz B,Zhou X,Liu D,Zhang Q,Ying QL

    更新日期:2015-09-08 00:00:00

  • Exercise-Induced Activated Platelets Increase Adult Hippocampal Precursor Proliferation and Promote Neuronal Differentiation.

    abstract::Physical activity is a strong positive physiological modulator of adult neurogenesis in the hippocampal dentate gyrus. Although the underlying regulatory mechanisms are still unknown, systemic processes must be involved. Here we show that platelets are activated after acute periods of running, and that activated plate...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2019.02.009

    authors: Leiter O,Seidemann S,Overall RW,Ramasz B,Rund N,Schallenberg S,Grinenko T,Wielockx B,Kempermann G,Walker TL

    更新日期:2019-04-09 00:00:00

  • ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons.

    abstract::Heterozygous mutations in the glucocerebrosidase gene (GBA) represent the strongest common genetic risk factor for Parkinson's disease (PD), the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independe...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2016.01.013

    authors: Fernandes HJ,Hartfield EM,Christian HC,Emmanoulidou E,Zheng Y,Booth H,Bogetofte H,Lang C,Ryan BJ,Sardi SP,Badger J,Vowles J,Evetts S,Tofaris GK,Vekrellis K,Talbot K,Hu MT,James W,Cowley SA,Wade-Martins R

    更新日期:2016-03-08 00:00:00

  • Structural phenotyping of stem cell-derived cardiomyocytes.

    abstract::Structural phenotyping based on classical image feature detection has been adopted to elucidate the molecular mechanisms behind genetically or pharmacologically induced changes in cell morphology. Here, we developed a set of 11 metrics to capture the increasing sarcomere organization that occurs intracellularly during...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2015.01.020

    authors: Pasqualini FS,Sheehy SP,Agarwal A,Aratyn-Schaus Y,Parker KK

    更新日期:2015-03-10 00:00:00

  • Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability.

    abstract::Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2017.10.015

    authors: Muratore CR,Zhou C,Liao M,Fernandez MA,Taylor WM,Lagomarsino VN,Pearse RV 2nd,Rice HC,Negri JM,He A,Srikanth P,Callahan DG,Shin T,Zhou M,Bennett DA,Noggle S,Love JC,Selkoe DJ,Young-Pearse TL

    更新日期:2017-12-12 00:00:00

  • Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells.

    abstract::Self-renewal potential and multipotency are hallmarks of a stem cell. It is generally accepted that acquisition of such stemness requires rejuvenation of somatic cells through reprogramming of their genetic and epigenetic status.We show here that a simple block of cell differentiation is sufficient to induce and maint...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2015.09.012

    authors: Ikawa T,Masuda K,Huijskens MJAJ,Satoh R,Kakugawa K,Agata Y,Miyai T,Germeraad WTV,Katsura Y,Kawamoto H

    更新日期:2015-11-10 00:00:00

  • A Cdx4-Sall4 regulatory module controls the transition from mesoderm formation to embryonic hematopoiesis.

    abstract::Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with g...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2013.10.001

    authors: Paik EJ,Mahony S,White RM,Price EN,Dibiase A,Dorjsuren B,Mosimann C,Davidson AJ,Gifford D,Zon LI

    更新日期:2013-11-07 00:00:00

  • A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.

    abstract::Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-b...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2018.11.015

    authors: Cohn R,Thakar K,Lowe A,Ladha FA,Pettinato AM,Romano R,Meredith E,Chen YS,Atamanuk K,Huey BD,Hinson JT

    更新日期:2019-01-08 00:00:00

  • Quick Commitment and Efficient Reprogramming Route of Direct Induction of Retinal Ganglion Cell-like Neurons.

    abstract::Direct reprogramming has been widely explored to generate various types of neurons for neurobiological research and translational medicine applications, but there is still no efficient reprogramming method to generate retinal ganglion cell (RGC)-like neurons, which are the sole projection neurons in the retina. Here, ...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.09.008

    authors: Wang J,He Q,Zhang K,Sun H,Zhang G,Liang H,Guo J,Hao L,Ke J,Chen S

    更新日期:2020-11-10 00:00:00

  • Directed Differentiation of Human Pluripotent Stem Cells to Microglia.

    abstract::Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microgl...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2017.04.023

    authors: Douvaras P,Sun B,Wang M,Kruglikov I,Lallos G,Zimmer M,Terrenoire C,Zhang B,Gandy S,Schadt E,Freytes DO,Noggle S,Fossati V

    更新日期:2017-06-06 00:00:00

  • BACE1 Deficiency Causes Abnormal Neuronal Clustering in the Dentate Gyrus.

    abstract::BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ)....

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2017.05.030

    authors: Hou H,Fan Q,He W,Suh H,Hu X,Yan R

    更新日期:2017-07-11 00:00:00

  • Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.

    abstract::In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous Kit(Wv) mutations into C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS) strongly promoted human multi-lineage reconstitution. After xenotransplantation of h...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2016.07.002

    authors: Yurino A,Takenaka K,Yamauchi T,Nunomura T,Uehara Y,Jinnouchi F,Miyawaki K,Kikushige Y,Kato K,Miyamoto T,Iwasaki H,Kunisaki Y,Akashi K

    更新日期:2016-09-13 00:00:00

  • Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies.

    abstract::The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiP...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2018.10.019

    authors: Negoro R,Takayama K,Kawai K,Harada K,Sakurai F,Hirata K,Mizuguchi H

    更新日期:2018-12-11 00:00:00

  • Sox100B Regulates Progenitor-Specific Gene Expression and Cell Differentiation in the Adult Drosophila Intestine.

    abstract::Robust production of terminally differentiated cells from self-renewing resident stem cells is essential to maintain proper tissue architecture and physiological functions, especially in high-turnover tissues. However, the transcriptional networks that precisely regulate cell transition and differentiation are poorly ...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.01.003

    authors: Meng FW,Rojas Villa SE,Biteau B

    更新日期:2020-02-11 00:00:00

  • LincU Preserves Naïve Pluripotency by Restricting ERK Activity in Embryonic Stem Cells.

    abstract::Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit ...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2018.06.010

    authors: Jiapaer Z,Li G,Ye D,Bai M,Li J,Guo X,Du Y,Su D,Jia W,Chen W,Wang G,Yu Y,Zhu F,Wan X,Kang J

    更新日期:2018-08-14 00:00:00

  • FAM122A Inhibits Erythroid Differentiation through GATA1.

    abstract::FAM122A is a highly conserved housekeeping gene, but its physiological and pathophysiological roles remain greatly elusive. Based on the fact that FAM122A is highly expressed in human CD71+ early erythroid cells, herein we report that FAM122A is downregulated during erythroid differentiation, while its overexpression ...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.07.010

    authors: Chen J,Zhou Q,Liu MH,Yang YS,Wang YQ,Huang Y,Chen GQ

    更新日期:2020-09-08 00:00:00

  • Developmental IL-6 Exposure Favors Production of PDGF-Responsive Multipotential Progenitors at the Expense of Neural Stem Cells and Other Progenitors.

    abstract::Interleukin-6 (IL-6) is increased in maternal serum and amniotic fluid of children subsequently diagnosed with autism spectrum disorders. However, it is not clear how increased IL-6 alters brain development. Here, we show that IL-6 increases the prevalence of a specific platelet-derived growth factor (PDGF)-responsive...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.03.019

    authors: Kumari E,Velloso FJ,Nasuhidehnavi A,Somasundaram A,Savanur VH,Buono KD,Levison SW

    更新日期:2020-05-12 00:00:00

  • PGC Reversion to Pluripotency Involves Erasure of DNA Methylation from Imprinting Control Centers followed by Locus-Specific Re-methylation.

    abstract::Primordial germ cells (PGCs) are fate restricted to differentiate into gametes in vivo. However, when removed from their embryonic niche, PGCs undergo reversion to pluripotent embryonic germ cells (EGCs) in vitro. One of the major differences between EGCs and embryonic stem cells (ESCs) is variable methylation at impr...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2015.07.006

    authors: Oliveros-Etter M,Li Z,Nee K,Hosohama L,Hargan-Calvopina J,Lee SA,Joti P,Yu J,Clark AT

    更新日期:2015-09-08 00:00:00

  • Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation.

    abstract::The bile salt export pump (BSEP) is responsible for the export of bile acid from hepatocytes. Impaired transcellular transport of bile acids in hepatocytes with mutations in BSEP causes cholestasis. Compensatory mechanisms to regulate the intracellular bile acid concentration in human hepatocytes with BSEP deficiency ...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.12.008

    authors: Hayashi H,Osaka S,Sakabe K,Fukami A,Kishimoto E,Aihara E,Sabu Y,Mizutani A,Kusuhara H,Naritaka N,Zhang W,Huppert SS,Sakabe M,Nakamura T,Hu YC,Mayhew C,Setchell K,Takebe T,Asai A

    更新日期:2020-12-30 00:00:00

  • A method to identify and isolate pluripotent human stem cells and mouse epiblast stem cells using lipid body-associated retinyl ester fluorescence.

    abstract::We describe the use of a characteristic blue fluorescence to identify and isolate pluripotent human embryonic stem cells and human-induced pluripotent stem cells. The blue fluorescence emission (450-500 nm) is readily observed by fluorescence microscopy and correlates with the expression of pluripotency markers (OCT4,...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2014.05.004

    authors: Muthusamy T,Mukherjee O,Menon R,Megha PB,Panicker MM

    更新日期:2014-06-12 00:00:00

  • Generation of foxn1/Casper Mutant Zebrafish for Allograft and Xenograft of Normal and Malignant Cells.

    abstract::Cell transplantation into immunodeficient recipients is a widely used approach to study stem cell and cancer biology; however, studying cell states post transplantation in vivo is inconvenient in mammals. Here, we generated a foxn1/Casper mutant zebrafish that is transparent and exhibits T cell deficiency. By employin...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.07.020

    authors: Lv P,Ma D,Gao S,Zhang Y,Bae YK,Liang G,Gao S,Choi JH,Kim CH,Wang L,Liu F

    更新日期:2020-09-08 00:00:00

  • Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis.

    abstract::Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the poss...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2017.02.015

    authors: Kruitwagen HS,Oosterhoff LA,Vernooij IGWH,Schrall IM,van Wolferen ME,Bannink F,Roesch C,van Uden L,Molenaar MR,Helms JB,Grinwis GCM,Verstegen MMA,van der Laan LJW,Huch M,Geijsen N,Vries RG,Clevers H,Rothuizen J,Schota

    更新日期:2017-04-11 00:00:00

  • Transgenesis and Genome Editing of Mouse Spermatogonial Stem Cells by Lentivirus Pseudotyped with Sendai Virus F Protein.

    abstract::Spermatogonial stem cells (SSCs) serve as a resource for producing genetically modified animals. However, genetic manipulation of SSCs has met with limited success. Here, we show efficient gene transfer into SSCs via a lentivirus (FV-LV) using a fusion protein (F), a Sendai virus (SV) envelope protein involved in viri...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2020.02.001

    authors: Shinohara T,Kanatsu-Shinohara M

    更新日期:2020-03-10 00:00:00

  • Modeling Developmental and Tumorigenic Aspects of Trilateral Retinoblastoma via Human Embryonic Stem Cells.

    abstract::Human embryonic stem cells (hESCs) provide a platform for studying human development and understanding mechanisms underlying diseases. Retinoblastoma-1 (RB1) is a key regulator of cell cycling, of which biallelic inactivation initiates retinoblastoma, the most common congenital intraocular malignancy. We developed a m...

    journal_title:Stem cell reports

    pub_type: 杂志文章

    doi:10.1016/j.stemcr.2017.03.005

    authors: Avior Y,Lezmi E,Yanuka D,Benvenisty N

    更新日期:2017-05-09 00:00:00