Article
|
Open Access
Featured
-
-
Article
| Open AccessTransient naive reprogramming corrects hiPS cells functionally and epigenetically
A new reprogramming strategy used to produce human induced pluripotent stem cells from somatic cells results in epigenetic and functional profiles that are highly similar to those of human embryonic stem cells.
- Sam Buckberry
- , Xiaodong Liu
- & Ryan Lister
-
Article |
KRAS(G12D) drives lepidic adenocarcinoma through stem-cell reprogramming
A study identifies the AT1 cell as a cell of origin for lung adenocarcinoma, and demonstrates that expression of oncogenic KRAS in differentiated AT1 cells reprograms them back into AT2 stem cells that generate indolent lepidic tumours.
- Nicholas H. Juul
- , Jung-Ki Yoon
- & Tushar J. Desai
-
Article |
Maternal inheritance of glucose intolerance via oocyte TET3 insufficiency
Pregestational hyperglycaemia in mothers increases the probability of glucose intolerance in the offspring, an effect controlled by TET3-dependent DNA demethylation of genes involved in insulin secretion.
- Bin Chen
- , Ya-Rui Du
- & Hefeng Huang
-
Article |
Chemical reprogramming of human somatic cells to pluripotent stem cells
Human somatic cells were reprogrammed to human chemically induced pluripotent stem cells that demonstrate key features of embryonic stem cells.
- Jingyang Guan
- , Guan Wang
- & Hongkui Deng
-
Article |
Modelling human blastocysts by reprogramming fibroblasts into iBlastoids
Human fibroblasts are reprogrammed to generate blastocyst-like structures called iBlastoids, which recapitulate aspects of embryo implantation.
- Xiaodong Liu
- , Jia Ping Tan
- & Jose M. Polo
-
Article |
Reprogramming to recover youthful epigenetic information and restore vision
Expression of three Yamanaka transcription factors in mouse retinal ganglion cells restores youthful DNA methylation patterns, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice, suggesting that mammalian tissues retain a record of youthful epigenetic information that can be accessed to improve tissue function.
- Yuancheng Lu
- , Benedikt Brommer
- & David A. Sinclair
-
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
-
Article |
Heterotypic cell–cell communication regulates glandular stem cell multipotency
The multipotency of basal stem cells is directly regulated by luminal cells through the secretion of TNF, and, following luminal cell ablation, the Notch, Wnt and EGFR signalling pathways reactivate basal cell multipotency.
- Alessia Centonze
- , Shuheng Lin
- & Cédric Blanpain
-
Article |
Pharmacologic fibroblast reprogramming into photoreceptors restores vision
A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.
- Biraj Mahato
- , Koray Dogan Kaya
- & Sai H. Chavala
-
Article |
Diabetes relief in mice by glucose-sensing insulin-secreting human α-cells
Islet non-β-cells from non-diabetic and diabetic human donors are modified via the transcription factors PDX1 and MAFA to produce and secrete insulin in response to glucose.
- Kenichiro Furuyama
- , Simona Chera
- & Pedro L. Herrera
-
Article |
Single-cell mapping of lineage and identity in direct reprogramming
Combinatorial tagging of single cells using expressed DNA barcodes, delivered by a lentiviral vector, is used to track individual cells and reconstruct their lineages and trajectories during cell fate reprogramming.
- Brent A. Biddy
- , Wenjun Kong
- & Samantha A. Morris
-
Article |
Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration
Reversion of adult skeletal stem cells to a developmental state underlies the growth of new bone during jaw regeneration, in a process that relies on mechanotransduction via the focal adhesion kinase protein.
- Ryan C. Ransom
- , Ava C. Carter
- & Michael T. Longaker
-
Letter |
Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
Müller glia in mature mouse retina can be stimulated to produce rod cells; this treatment restores visual responses in a model of congenital blindness.
- Kai Yao
- , Suo Qiu
- & Bo Chen
-
Letter |
Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte
Gonadal germline epigenetic reprogramming involves an interplay between DNA methylation, the polycomb complex and Tet1 in both DNA methylation dependent and independent roles, to ensure the activation of a specific subset of genes critical for progression of gametogenesis.
- Peter W. S. Hill
- , Harry G. Leitch
- & Petra Hajkova
-
Letter |
Single-cell transcriptomics reconstructs fate conversion from fibroblast to cardiomyocyte
Single-cell transcriptomics analyses of cell intermediates during the reprogramming from fibroblast to cardiomyocyte were used to reconstruct the reprogramming trajectory and to uncover intermediate cell populations, gene pathways and regulators involved in this process.
- Ziqing Liu
- , Li Wang
- & Li Qian
-
Letter |
Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates
The neuron-specific transcription factor Myt1l represses many somatic lineage programs, but not the neuronal lineage program, to both induce and maintain neuronal identity.
- Moritz Mall
- , Michael S. Kareta
- & Marius Wernig
-
Letter |
Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition
Using a single-nucleus Hi-C protocol, the authors find that spatial organization of chromatin during oocyte-to-zygote transition differs between paternal and maternal nuclei within a single-cell zygote.
- Ilya M. Flyamer
- , Johanna Gassler
- & Kikuë Tachibana-Konwalski
-
Letter |
Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition
Three papers in this issue of Nature use highly sensitive ChIP–seq assays to describe the dynamic patterns of histone modifications during early mouse embryogenesis, showing that oocytes have a distinctive epigenome and providing insights into how the maternal gene expression program transitions to the zygotic program.
- John Arne Dahl
- , Inkyung Jung
- & Arne Klungland
-
Letter |
A human neurodevelopmental model for Williams syndrome
A human neurodevelopmental model fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.
- Thanathom Chailangkarn
- , Cleber A. Trujillo
- & Alysson R. Muotri
-
Letter |
Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq
The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.
- Barbara Treutlein
- , Qian Yi Lee
- & Stephen R. Quake
-
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
-
Letter |
Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung
Inhibitory antibodies to two specific human and mouse Notch ligands, Jagged1 and Jagged2, are generated and shown to have beneficial effects in a goblet cell metaplasia asthma model; systemic Jagged1 inhibition transdifferentiates secretory cells into ciliated cells in the mouse, demonstrating that Jagged1 from ciliated cells normally holds back secretory cells to adopt the ciliated fate.
- Daniel Lafkas
- , Amy Shelton
- & Christian W. Siebel
-
Brief Communications Arising |
Failure to replicate the STAP cell phenomenon
- Alejandro De Los Angeles
- , Francesco Ferrari
- & George Q. Daley
-
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
-
Article |
Divergent reprogramming routes lead to alternative stem-cell states
The forced expression of key transcription factors can induce somatic cells to acquire pluripotency characteristics; here high levels of reprogramming factors are used to induce mouse embryonic fibroblasts to a stable alternative pluripotent state with low intercellular adhesion.
- Peter D. Tonge
- , Andrew J. Corso
- & Andras Nagy
-
Letter |
Epigenetic reprogramming that prevents transgenerational inheritance of the vernalized state
The Arabidopsis thaliana floral repressor FLC is epigenetically silenced by prolonged cold in a process called vernalization and then is reactivated before the completion of seed development; a histone demethylase, ELF6, is now shown to be involved in reactivating FLC in reproductive tissues, allowing the resetting of FLC expression and thus the requirement for vernalization in each generation.
- Pedro Crevillén
- , Hongchun Yang
- & Caroline Dean
-
Letter |
The DNA methylation landscape of human early embryos
Base-resolution maps of DNA methylation in human gametes and early embryos offer novel insights into human methylation dynamics and the functional relationship between DNA methylation and gene expression.
- Hongshan Guo
- , Ping Zhu
- & Jie Qiao
-
Article |
Reprogramming human endothelial cells to haematopoietic cells requires vascular induction
This study describes the conversion of human fetal and adult vascular endothelial cells into engraftable haematopoietic progenitors by transduction with some transcription factors and then culture on a vascular niche feeder layer; the haematopoietic progenitors may be useful for the generation of engraftable healthy and long-lasting haematopoietic cells for treatment of inherited and acquired blood disorders.
- Vladislav M. Sandler
- , Raphael Lis
- & Shahin Rafii
-
Letter |
Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells
Here human embryonic stem cell lines are derived by somatic cell nuclear transfer from cells of a newborn and from skin cells of an adult, a female with type 1 diabetes; the stem cells produced are pluripotent and can be differentiated into insulin-producing beta cells.
- Mitsutoshi Yamada
- , Bjarki Johannesson
- & Dieter Egli
-
Letter |
Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos
Reprogramming after somatic cell nuclear transfer had been thought to be dependent on the recipient cytoplasm being arrested at the metaphase stage, but here interphase two-cell mouse embryos are shown to support successful reprogramming and generation of embryonic stem cells or cloned mice.
- Eunju Kang
- , Guangming Wu
- & Shoukhrat Mitalipov
-
Letter |
Mouse liver repopulation with hepatocytes generated from human fibroblasts
Human fibroblasts can be converted into hepatocytes capable of repopulating mouse livers by shortcutting reprogramming to pluripotency with factors promoting endoderm and hepatocyte differentiation.
- Saiyong Zhu
- , Milad Rezvani
- & Sheng Ding
-
Article |
RETRACTED ARTICLE: Stimulus-triggered fate conversion of somatic cells into pluripotency
One of two papers describing a reprogramming phenomenon called stimulus-triggered acquisition of pluripotency (STAP) — in STAP, lineage-committed adult somatic cells are reprogrammed to pluripotency by transient exposure to low-pH treatment, and extensive analysis of the molecular features and developmental potential of STAP cells indicates that they represent a unique state of pluripotency.
- Haruko Obokata
- , Teruhiko Wakayama
- & Charles A. Vacanti
-
Letter |
Citrullination regulates pluripotency and histone H1 binding to chromatin
This study shows that PADI4-mediated citrullination occurs during pluripotency and that citrullination of H1 results in loosening of chromatin compaction; furthermore, citrullination is shown to be important for the activation of stem-cell genes, for iPS cell reprogramming and to maintain pluripotent cells in the early mouse embryo.
- Maria A. Christophorou
- , Gonçalo Castelo-Branco
- & Tony Kouzarides
-
Letter |
Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells
Generation of human induced pluripotent stem cells from patient fibroblasts containing ring chromosomes with large deletions reveals that reprogrammed cells lose the abnormal chromosome and duplicate the wild-type homologue through compensatory uniparental disomy, suggesting that cellular reprogramming may hold potential for ‘chromosome therapy’.
- Marina Bershteyn
- , Yohei Hayashi
- & Anthony Wynshaw-Boris
-
Article |
Dedifferentiation of committed epithelial cells into stem cells in vivo
Using in vivo lineage tracing in mice and sorted cells in culture, the ability of stably committed cells to dedifferentiate into basal stem cells in the mouse trachea is investigated: the findings suggest that the dedifferentiation of committed cell types into stem cells may contribute generally to regeneration in higher vertebrates in different organ and injury contexts.
- Purushothama Rao Tata
- , Hongmei Mou
- & Jayaraj Rajagopal
-
Letter |
Derivation of novel human ground state naive pluripotent stem cells
It is known that human embryonic stem (ES) cells are more similar to mouse primed epiblast stem cells than to naive mouse ES cells; here culture conditions are determined that allow human ES and induced pluripotent stem cells to acquire a pluripotent state that retains growth characteristics highly similar to mouse naive ES cells, and competence in generating cross-species human-mouse embryonic chimaerism.
- Ohad Gafni
- , Leehee Weinberger
- & Jacob H. Hanna
-
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
-
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
-
Article |
Reprogramming in vivo produces teratomas and iPS cells with totipotency features
Induced pluripotent stem cells (iPS cells) have been created in vivo by reprogramming mouse somatic cells with Oct4, Sox2, Klf4 and c-Myc; these cells have totipotent features that are missing from in vitro created iPS cells or embryonic stem cells.
- María Abad
- , Lluc Mosteiro
- & Manuel Serrano
-
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
-
Letter |
High-resolution analysis with novel cell-surface markers identifies routes to iPS cells
Cellular reprogramming is shown to occur in an ordered, stepwise manner, marked by changes in the cell-surface markers CD44, ICAM1 and Nanog–eGFP; molecular characterization of discrete subpopulations of partially reprogrammed cells shows that reprogramming is not simply the reversal of the normal development process.
- James O’Malley
- , Stavroula Skylaki
- & Keisuke Kaji
-
Research Highlights |
Immune response spurs cell switch
-
Research Highlights |
Mouse eggs from stem cells
-
News |
Cell rewind wins medicine Nobel
Researchers awarded prestigious prize for their work on reprogramming mature cells to a pluripotent state.
- Alison Abbott
-
Research Highlights |
Salamanders heal like embryos grow
-
News & Views |
Actors in the cell reprogramming drama
The transformation of skin cells into stem cells is a fascinating but poorly understood process. At last, the molecular characters underlying the initial steps have been revealed. See Letter p.652
- Kyle M. Loh
- & Bing Lim
-
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
-
Letter |
The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming
The H3K27 demethylase Utx is reported to be a critical regulator for the initiation of somatic and germ cell reprogramming.
- Abed AlFatah Mansour
- , Ohad Gafni
- & Jacob H. Hanna
-
Article |
Heart repair by reprogramming non-myocytes with cardiac transcription factors
A combination of four transcription factors, GATA4, HAND2, MEF2C and TBX5, can reprogram fibroblasts into cardiac-like myocytes in vitro and in vivo; expression of these factors ameliorated cardiac function in mice that had suffered myocardial infarction.
- Kunhua Song
- , Young-Jae Nam
- & Eric N. Olson