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Co-transplantation of autologous Treg cells in a cell therapy for Parkinson’s disease
In mouse and rat models of Parkinson’s disease, co-transplanting regulatory T cells (Treg cells) improves the survival of grafted midbrain dopamine neurons in cell therapies by reducing the inflammatory response caused by surgical injury.
- Tae-Yoon Park
- , Jeha Jeon
- & Kwang-Soo Kim
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Article
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Integrated intracellular organization and its variations in human iPS cells
A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.
- Matheus P. Viana
- , Jianxu Chen
- & Susanne M. Rafelski
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Article |
Generation of 3D lacrimal gland organoids from human pluripotent stem cells
Organoids originating from human multipotent ocular surface epithelial stem cells are similar to native lacrimal glands and undergo functional maturation when transplanted adjacent to the eyes of recipient rats, developing lumina and producing tear-film proteins.
- Ryuhei Hayashi
- , Toru Okubo
- & Kohji Nishida
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Article |
Reprogramming roadmap reveals route to human induced trophoblast stem cells
Single-cell transcriptomics roadmap of human dermal fibroblasts reprogrammed to primed and naive pluripotency reveals a route for the direct reprogramming of somatic cells into induced trophoblast stem cells.
- Xiaodong Liu
- , John F. Ouyang
- & Jose M. Polo
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Article |
Intracellular pH controls WNT downstream of glycolysis in amniote embryos
The authors show that metabolic activity leads to an increase in the intracellular pH of neuromesodermal precursors, and that this increase in pH, by allowing post-translational modification of β-catenin, is required for the activation of WNT signalling and mesodermal fate acquisition.
- Masayuki Oginuma
- , Yukiko Harima
- & Olivier Pourquié
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Article |
Recapitulating the human segmentation clock with pluripotent stem cells
A system involving in vitro induction of presomitic mesoderm recapitulates oscillatory expression of core segmentation clock genes and travelling-wave-like gene expression, suggesting that this system can be used to study the human segmentation clock and provide insights into diseases associated with human axial skeletogenesis.
- Mitsuhiro Matsuda
- , Yoshihiro Yamanaka
- & Cantas Alev
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Article |
Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing
Fibroblasts from old mice are heterogeneous, which affects the ability of these fibroblasts to reprogram into induced pluripotent stem cells in vitro and influences wound healing rate in vivo.
- Salah Mahmoudi
- , Elena Mancini
- & Anne Brunet
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Letter |
An orthogonal proteomic survey uncovers novel Zika virus host factors
Integrative analyses identify host proteins that are modulated by Zika virus at multiple levels and provide a comprehensive framework for the understanding of Zika virus-induced changes to cellular pathways.
- Pietro Scaturro
- , Alexey Stukalov
- & Andreas Pichlmair
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Letter |
Advanced maturation of human cardiac tissue grown from pluripotent stem cells
A tissue culture system that provides an increasing intensity of electromechanical stimulation over time enables an in vitro model of cardiac tissue derived from human induced pluripotent stem cells to develop many of the characteristics of adult cardiac tissue.
- Kacey Ronaldson-Bouchard
- , Stephen P. Ma
- & Gordana Vunjak-Novakovic
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Letter |
Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model
In a preclinical study, dopaminergic neurons derived from human induced pluripotent stem cells were implanted into a primate model of Parkinson’s disease, where they were found to exhibit long-term survival, function as mid-brain dopaminergic neurons, and increase spontaneous movements.
- Tetsuhiro Kikuchi
- , Asuka Morizane
- & Jun Takahashi
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Article |
Common genetic variation drives molecular heterogeneity in human iPSCs
Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease.
- Helena Kilpinen
- , Angela Goncalves
- & Daniel J. Gaffney
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Article |
Cell diversity and network dynamics in photosensitive human brain organoids
Long-term cultures of human brain organoids display a high degree of cellular diversity, mature spontaneous neuronal networks and are sensitive to light.
- Giorgia Quadrato
- , Tuan Nguyen
- & Paola Arlotta
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Letter |
Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts
Allogenic induced pluripotent stem cell-derived cardiomyocytes transplanted directly into infarcted cynomolgus monkey hearts show electrical coupling with host cardiomyocytes improve cardiac contractile function after mild immunosuppression.
- Yuji Shiba
- , Toshihito Gomibuchi
- & Uichi Ikeda
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Letter |
Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9
A CRISPR/Cas9 genome editing framework has been developed that allows controlled introduction of mono- and bi-allelic sequence changes, and is used to generate induced human pluripotent stem cells with heterozygous and homozygous dominant mutations in amyloid precursor protein and presenilin 1 that have been associated with early onset Alzheimer’s disease.
- Dominik Paquet
- , Dylan Kwart
- & Marc Tessier-Lavigne
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Letter |
Co-ordinated ocular development from human iPS cells and recovery of corneal function
A protocol has been developed to use human induced pluripotent stem cells to obtain a self-formed ectodermal autonomous multizone, which includes distinct cell lineages of the eye, including the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium that can be expanded to form a functional corneal epithelium when transplanted to an animal model of corneal visual impairment.
- Ryuhei Hayashi
- , Yuki Ishikawa
- & Kohji Nishida
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Article |
The histone chaperone CAF-1 safeguards somatic cell identity
RNA interference screens were used to identify chromatin-associated factors that impede reprogramming of somatic cells into iPS cells; suppression of the chromatin assembly factor CAF-1 enhances the generation of iPS cells by rendering chromatin more accessible to pluripotency transcription factors.
- Sihem Cheloufi
- , Ulrich Elling
- & Konrad Hochedlinger
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Letter |
Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder
A neuronal model of bipolar disorder based on induced pluripotent stem cell (iPSC) technology finds hyperactive action-potential firing and differential responsiveness to lithium in iPSC-derived neurons from patients with bipolar disorder.
- Jerome Mertens
- , Qiu-Wen Wang
- & Jun Yao
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Brief Communications Arising |
Failure to replicate the STAP cell phenomenon
- Alejandro De Los Angeles
- , Francesco Ferrari
- & George Q. Daley
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Brief Communications Arising |
STAP cells are derived from ES cells
- Daijiro Konno
- , Takeya Kasukawa
- & Fumio Matsuzaki
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Review Article |
Hallmarks of pluripotency
In response to the need for a defined set of criteria to assess stem-cell potency, this review proposes guidelines for the evaluation of newly derived pluripotent stem cells, from functional assays to integrative molecular analyses of transcriptional, epigenetic and metabolic states.
- Alejandro De Los Angeles
- , Francesco Ferrari
- & George Q. Daley
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Article |
An alternative pluripotent state confers interspecies chimaeric competency
A previously unknown type of stem cell that can engraft in specific regions of the mouse epiblast is described; these region-selective pluripotent stem cells display notable intra- and inter-specific chimaera competency and will help to further our understanding of mammalian development.
- Jun Wu
- , Daiji Okamura
- & Juan Carlos Izpisua Belmonte
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Letter |
Early reprogramming regulators identified by prospective isolation and mass cytometry
Identification of transient early induced pluripotency reprogramming intermediates allows for mechanistic insight into the reprogramming process.
- Ernesto Lujan
- , Eli R. Zunder
- & Marius Wernig
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Article |
Genome-wide characterization of the routes to pluripotency
This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.
- Samer M. I. Hussein
- , Mira C. Puri
- & Andras Nagy
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Article |
Statin treatment rescues FGFR3 skeletal dysplasia phenotypes
This study reprograms fibroblasts from thanatophoric dysplasia type I (TD1) and achondroplasia (ACH) patients into induced pluripotent stem cells (iPSCs), finding that chondrogenic differentiation results in the formation of degraded cartilage; statin treatment led to significant recovery of bone growth in a mouse model of ACH.
- Akihiro Yamashita
- , Miho Morioka
- & Noriyuki Tsumaki
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Letter |
C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells
A pulse of C/EBPα followed by overexpression of the transcription factors Oct4, Sox2, Klf4 and Myc leads to fast and very efficient reprogramming of B cell precursors to induced pluripotent stem cells; C/EBPα facilitates transient chromatin accessibility and accelerates expression of pluripotency genes through a mechanism that involves activation of the Tet2 enzyme.
- Bruno Di Stefano
- , Jose Luis Sardina
- & Thomas Graf
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Letter |
Differential L1 regulation in pluripotent stem cells of humans and apes
Induced pluripotent stem-cell characterization reveals phenotypical differences between humans and non-human primates (NHPs): gene expression analysis shows differences in the regulation of long interspersed element-1 (L1) transposons, and in the expression of L1-restricting genes APOBEC3B and PIWIL2, correlating with higher L1 mobility in NHPs; this indicates that L1 mobility differences may have differentially shaped the human and NHP genomes.
- Maria C. N. Marchetto
- , Iñigo Narvaiza
- & Fred H. Gage
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Article |
Deterministic direct reprogramming of somatic cells to pluripotency
This study shows that the combination of naive pluripotency growth conditions, Oct4, Sox2, Klf4 and Myc (OSKM) overexpression, and depleting the Mbd3/NuRD co-repressor results in deterministic and synchronized reprogramming to pluripotency.
- Yoach Rais
- , Asaf Zviran
- & Jacob H. Hanna
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Letter |
Vascularized and functional human liver from an iPSC-derived organ bud transplant
Vascularized, functional human liver is generated from human induced pluripotent stem cells (iPSCs) by transplantation of liver buds created in vitro (iPSC-LBs); hepatic cells self-organized into three-dimensional iPSC-LBs, and human vasculatures in iPSC-LB transplants became functional by connecting to host vessels, stimulating maturation of iPSC-LBs into tissue resembling adult liver and performing liver-specific functions.
- Takanori Takebe
- , Keisuke Sekine
- & Hideki Taniguchi
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Letter |
AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes
Fibroblasts deficient in the activation-induced cytidine deaminase (AID) enzyme are shown to fail to stabilize in the pluripotent state, despite initiating the expression of pluripotency genes.
- Ritu Kumar
- , Lauren DiMenna
- & Todd Evans
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Letter |
NANOG-dependent function of TET1 and TET2 in establishment of pluripotency
The authors show that the pluripotency factor NANOG interacts with TET1 and TET2 methylcytosine hydroxylases, and that the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine enhances the efficiency of somatic cell reprogramming in a NANOG-dependent manner.
- Yael Costa
- , Junjun Ding
- & Jianlong Wang
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Letter |
Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs
This study demonstrates that an inheritable adult onset heart disease can be modelled in vitro within months with the help of metabolic maturation induction.
- Changsung Kim
- , Johnson Wong
- & Huei-Sheng Vincent Chen
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Letter |
Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells
Immune rejection may limit the therapeutic use of induced pluripotent stem cells (iPSCs); here, terminally differentiated mouse iPSCs are shown to generate negligible immune rejection in their host.
- Ryoko Araki
- , Masahiro Uda
- & Masumi Abe
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News |
Brain cells made from urine
Human excreta could be a powerful source of cells to study disease, bypassing some of the problems of using stem cells.
- Monya Baker
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Letter |
Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells
A whole-genome and transcriptome analysis of 20 human induced pluripotent stem-cell lines shows that reprogramming does not necessarily add de novo copy number variants to what is already present in the somatic cells from which they originated.
- Alexej Abyzov
- , Jessica Mariani
- & Flora M. Vaccarino
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News |
Stem-cell transplant claims debunked
Transplant of induced pluripotent stem cells to treat heart failure probably never happened.
- David Cyranoski
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Letter |
Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2
Parp1 and Tet2 mediate essential epigenetic remodelling events in an early phase of induced pluripotent stem cell reprogramming, thus directing subsequent induction of the pluripotency loci.
- Claudia A. Doege
- , Keiichi Inoue
- & Asa Abeliovich
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News |
Stem-cell pioneer banks on future therapies
Japanese researcher plans cache of induced stem cells to supply clinical trials.
- David Cyranoski
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News |
Rudimentary liver grown in vitro
Japanese scientists coax pluripotent cells to form functional liver tissue.
- David Cyranoski
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News |
Alzheimer's 'in a dish' shows promise
Reprogrammed cells suggest path towards early diagnosis and drug development.
- Ewen Callaway
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Letter |
Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells
Induced pluripotent stem cells are shown to be useful for studying phenotypes relevant to familial and sporadic Alzheimer’s disease, even though it can take decades for the disease to manifest in patients.
- Mason A. Israel
- , Shauna H. Yuan
- & Lawrence S. B. Goldstein
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Review Article |
The promise of induced pluripotent stem cells in research and therapy
- Daisy A. Robinton
- & George Q. Daley
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Letter |
Excitation-induced ataxin-3 aggregation in neurons from patients with Machado–Joseph disease
Human neurons derived from induced pluripotent stem cells permit the study of aberrant protein processing and aggregation in Machado–Joseph disease.
- Philipp Koch
- , Peter Breuer
- & Oliver Brüstle
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News |
Liver-disease mutation corrected in human stem cells
Patient-derived stem cells reprogrammed to become healthier.
- Susan Young
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Letter |
Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells
- Kosuke Yusa
- , S. Tamir Rashid
- & Ludovic Vallier
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News & Views |
iPS cells under attack
Induced pluripotent stem cells offer promise for patient-specific regenerative therapy. But a study now cautions that, even when immunologically matched, these cells can be rejected after transplantation. See Letter p.212
- Effie Apostolou
- & Konrad Hochedlinger
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Letter |
Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1
- Momoko Maekawa
- , Kei Yamaguchi
- & Shinya Yamanaka
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Letter |
Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells
- Luis F. Z. Batista
- , Matthew F. Pech
- & Steven E. Artandi
Complete human day 14 post-implantation embryo models from naive ES cells
Pancreas regeneration