Single-Cell Profiling Identifies Key Pathways Expressed by iPSCs Cultured in Different Commercial Media.
AuthorsDaniszewski M, Nguyen Q, Chy HS, Singh V, Crombie DE, Kulkarni T, Liang HH, Sivakumaran P, Lidgerwood GE, Hernández D, Conquest A, Rooney LA, Chevalier S, Andersen SB, Senabouth A, Vickers JC, Mackey DA, Craig JE, Laslett AL, Hewitt AW, Powell JE, Pébay A
JournaliScience
PubMed ID30267684
'We assessed the pluripotency of human induced pluripotent stem cells (iPSCs) maintained on an automated platform using StemFlex and TeSR-E8 media. Analysis of transcriptome of single cells revealed similar expression of core pluripotency genes, as well as genes associated with naive and primed states of pluripotency. Analysis of individual cells ... More
Improving single-cell cloning workflow for gene editing in human pluripotent stem cells.
AuthorsChen YH, Pruett-Miller SM
JournalStem Cell Res
PubMed ID30099335
'The availability of human pluripotent stem cells (hPSCs) and progress in genome engineering technology have altered the way we approach scientific research and drug development screens. Unfortunately, the procedures for genome editing of hPSCs often subject cells to harsh conditions that compromise viability: a major problem that is compounded by ... More
Detection of Deleterious On-Target Effects after HDR-Mediated CRISPR Editing.
AuthorsWeisheit I, Kroeger JA, Malik R, Klimmt J, Crusius D, Dannert A, Dichgans M, Paquet D
JournalCell Rep
PubMed ID32460021
'CRISPR genome editing is a promising tool for translational research but can cause undesired editing outcomes, both on target at the edited locus and off target at other genomic loci. Here, we investigate the occurrence of deleterious on-target effects (OnTEs) in human stem cells after insertion of disease-related mutations by ... More
Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells.
AuthorsChen SW, Himeno M, Koui Y, Sugiyama M, Nishitsuji H, Mizokami M, Shimotohno K, Miyajima A, Kido T
JournalSci Rep
PubMed ID32873852
'Hepatocytes derived from human iPSCs are useful to study hepatitis B virus (HBV) infection, however infection efficiency is rather poor. In order to improve the efficiency of HBV infection to iPSC-derived hepatocytes, we set a co-culture of hepatocytes with liver non-parenchymal cells and found that liver sinusoidal endothelial cells (LSECs) ... More
A Simple Procedure for Creating Scalable Phenotypic Screening Assays in Human Neurons.
AuthorsSridharan B, Hubbs C, Llamosas N, Kilinc M, Singhera FU, Willems E, Piper DR, Scampavia L, Rumbaugh G, Spicer TP
JournalSci Rep
PubMed ID31227747
'Neurons created from human induced pluripotent stem cells (hiPSCs) provide the capability of identifying biological mechanisms that underlie brain disorders. IPSC-derived human neurons, or iNs, hold promise for advancing precision medicine through drug screening, though it remains unclear to what extent iNs can support early-stage drug discovery efforts in industrial-scale ... More
Ultrasensitive and rapid quantification of rare tumorigenic stem cells in hPSC-derived cardiomyocyte populations.
AuthorsWang Z, Gagliardi M, Mohamadi RM, Ahmed SU, Labib M, Zhang L, Popescu S, Zhou Y, Sargent EH, Keller GM, Kelley SO
JournalSci Adv
PubMed ID32440533
The ability to detect rare human pluripotent stem cells (hPSCs) in differentiated populations is critical for safeguarding the clinical translation of cell therapy, as these undifferentiated cells have the capacity to form teratomas in vivo. The detection of hPSCs must be performed using an approach compatible with traceable manufacturing of ... More
Cell stress in cortical organoids impairs molecular subtype specification.
AuthorsBhaduri A, Andrews MG, Mancia Leon W, Jung D, Shin D, Allen D, Jung D, Schmunk G, Haeussler M, Salma J, Pollen AA, Nowakowski TJ, Kriegstein AR
JournalNature
PubMed ID31996853
Cortical organoids are self-organizing three-dimensional cultures that model features of the developing human cerebral cortex
Metabolic Regulation of Inflammasome Activity Controls Embryonic Hematopoietic Stem and Progenitor Cell Production.
AuthorsFrame JM, Kubaczka C, Long TL, Esain V, Soto RA, Hachimi M, Jing R, Shwartz A, Goessling W, Daley GQ, North TE
JournalDev Cell
PubMed ID32810442
Embryonic hematopoietic stem and progenitor cells (HSPCs) robustly proliferate while maintaining multilineage potential in vivo; however, an incomplete understanding of spatiotemporal cues governing their generation has impeded robust production from human induced pluripotent stem cells (iPSCs) in vitro. Using the zebrafish model, we demonstrate that NLRP3 inflammasome-mediated interleukin-1-beta (IL1ß) signaling drives HSPC ... More
Interferon-? signaling in human iPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes.
AuthorsWarre-Cornish K, Perfect L, Nagy R, Duarte RRR, Reid MJ, Raval P, Mueller A, Evans AL, Couch A, Ghevaert C, McAlonan G, Loth E, Murphy D, Powell TR, Vernon AC, Srivastava DP, Price J
JournalSci Adv
PubMed ID32875100
Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-? (IFN-?), in offspring's brains play a central role. IFN-? activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-? is implicated in brain development. We tested the hypothesis that IFN-? signaling contributes to molecular ... More
A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.
AuthorsYang L, Han Y, Nilsson-Payant BE, Gupta V, Wang P, Duan X, Tang X, Zhu J, Zhao Z, Jaffré F, Zhang T, Kim TW, Harschnitz O, Redmond D, Houghton S, Liu C, Naji A, Ciceri G, Guttikonda S, Bram Y, Nguyen DT, Cioffi M, Chandar V, Hoagland DA, Huang Y, Xiang J, Wang H, Lyden D, Borczuk A, Chen HJ, Studer L, Pan FC, Ho DD, tenOever BR, Evans T, Schwartz RE, Chen S
JournalCell Stem Cell
PubMed ID32579880
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from ... More