Featured
-
-
Article
| Open AccessTranscriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution
Limb regeneration requires a blastema with progenitor cells, immune cells, and an overlying wound epidermis, but molecular identities of these populations are unclear. Here, the authors use single-cell RNA-sequencing to identify transcriptionally distinct cell populations in adult axolotl limb blastemas.
- Nicholas D. Leigh
- , Garrett S. Dunlap
- & Jessica L. Whited
-
Article
| Open AccessHoney bee Royalactin unlocks conserved pluripotency pathway in mammals
Royal jelly is the queen-maker for the honey bee that also has effects on longevity, fertility, and regeneration in mammals. Here the authors provide evidence that its major protein component Royalactin, and the mammalian structural analog Regina, maintain pluripotency in mouse ESCs by activating a ground-state pluripotency-like gene network.
- Derrick C. Wan
- , Stefanie L. Morgan
- & Kevin C. Wang
-
Article
| Open AccessMTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells
Reprogramming of mitochondria metabolism occurs during naïve to primed pluripotency differentiation in mouse embryonic stem cells (ESCs). Here the authors show that mitochondrial MTCH2 regulates mitochondrial fusion and that this fusion is required for naïve to primed pluripotency conversion
- Amir Bahat
- , Andres Goldman
- & Atan Gross
-
Article
| Open AccessIslr regulates canonical Wnt signaling-mediated skeletal muscle regeneration by stabilizing Dishevelled-2 and preventing autophagy
“Satellite cells are crucial for skeletal muscle regeneration. Here the authors show that immunoglobulin superfamily containing leucine-rich repeat (Islr) promotes skeletal muscle regeneration via a mechanism involving Dishevelled-2 stabilization in satellite cells and protection from autophagy.
- Kuo Zhang
- , Yuying Zhang
- & Qingyong Meng
-
Article
| Open AccessRobo signalling controls pancreatic progenitor identity by regulating Tead transcription factors
A role for Slit/Robo signalling in pancreas development has not been defined. Here, the authors generate Robo1/Robo2 knockout mice to identify both as needed for establishing initial pancreatic cell identity as well as for proliferation and survival of pancreatic progenitors.
- Sophie Escot
- , David Willnow
- & Francesca M. Spagnoli
-
Article
| Open AccessShavenbaby and Yorkie mediate Hippo signaling to protect adult stem cells from apoptosis
Organ regeneration by stem cells is required to compensate for tissue damage during aging, although how stem cells are maintained in adulthood is poorly understood. Here, the authors show in Drosophila that Shavenbaby interacts with Yorkie, a mediator of Hippo signalling, to ensure adult stem cell survival.
- Jérôme Bohère
- , Alexandra Mancheno-Ferris
- & François Payre
-
Article
| Open AccessDefining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis
Human induced pluripotent stem cell derived cardiomyocytes are a powerful model for cardiogenesis and disease in vitro. Here the authors comprehensively map cardiac differentiation using multiple modalities, including single-cell RNA seq and CyTOF, in cells with a gain or loss of function in key cardiac transcription factors.
- Jared M. Churko
- , Priyanka Garg
- & Joseph C. Wu
-
Article
| Open AccessSingle cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement
Cardiac progenitor cells (CPCs) form cardiomyocytes, pericytes, smooth muscle and endothelial cells during embryonic development. Here, the authors characterize mouse CPCs marked by Nkx2.5 and Isl1 from E7.5 to E9.5 by single cell RNA-seq and ATAC-seq, showing fate transitions involve distinct open chromatin state.
- Guangshuai Jia
- , Jens Preussner
- & Thomas Braun
-
Article
| Open AccessAge-related declines in α-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration
While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.
- A. Sahu
- , H. Mamiya
- & F. Ambrosio
-
Article
| Open AccessH3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression
The effects of epigenetic regulators on different tumor cell populations can affect their potential as anticancer targets. In this study, the authors demonstrate that the histone methyltransferase G9a is a suppressor of lung tumor-propagating cells and tumor progression, acting through chromatin modification with MMP10 as one of its targets for metastasis regulation.
- S. P. Rowbotham
- , F. Li
- & C. F. Kim
-
Article
| Open AccessA hPSC-based platform to discover gene-environment interactions that impact human β-cell and dopamine neuron survival
Diseases such as diabetes and Parkinson's manifest based on interactions between genes and environment. Here, the authors find among a panel of cell types that propargite, a common pesticide, induces pancreatic β-cell and dopamine neuron death and that loss of the gene GSTT1 confers hypersensitivity.
- Ting Zhou
- , Tae Wan Kim
- & Shuibing Chen
-
Article
| Open AccessMettl3-mediated m6A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis
mRNA modifications have been shown to regulate mammalian development and disease. Here the authors show that the m6A methyltransferase Mettl3 ensures translational efficiency of the mesenchymal stem cell lineage allocator Pth1r, promoting osteogenesis and protecting from osteoporosis.
- Yunshu Wu
- , Liang Xie
- & Quan Yuan
-
Article
| Open AccessARTS mediates apoptosis and regeneration of the intestinal stem cell niche
The mechanisms regulating intestinal stem cell elimination remain unclear. Here, the authors identify that the pro-apoptotic protein ARTS (a Septin4 isoform) interacts with XIAP in the intestinal stem cell niche to regulate stem cell survival during intestinal homeostasis and regeneration.
- Elle Koren
- , Yahav Yosefzon
- & Yaron Fuchs
-
Article
| Open AccessNuRD-interacting protein ZFP296 regulates genome-wide NuRD localization and differentiation of mouse embryonic stem cells
The NuRD complex plays an important role in regulating lineage commitment and cell fate during early embryonic development. Here the authors present an integrative analysis of MBD3/NuRD composition and binding in mouse embryonic stem cells and neural progenitor cells, providing a molecular basis for genome-wide NuRD localization
- Susan L. Kloet
- , Ino D. Karemaker
- & Michiel Vermeulen
-
Article
| Open AccessBiologically relevant laminin as chemically defined and fully human platform for human epidermal keratinocyte culture
In vitro expansion of human epidermal keratinocytes to resurface severe wound defects still relies on a human/mouse xenograft culture system. Here the authors develop a fully human, xeno-free culture system using skin-associated laminins, normally present in vivo, to replace mouse feeder cells.
- Monica Suryana Tjin
- , Alvin Wen Choong Chua
- & Karl Tryggvason
-
Article
| Open AccessSpatiotemporal regulation of the GPCR activity of BAI3 by C1qL4 and Stabilin-2 controls myoblast fusion
Myoblast fusion is an essential step in muscle growth and regeneration, and is regulated by the G-protein coupled receptor (GPCR) BAI3. Here Hamoud et al. show that the GPCR activity of BAI3 is spatiotemporally regulated during myoblast fusion, and identify C1qL4 and Stabilin-2 as, respectively, negative and positive regulators of its activity.
- Noumeira Hamoud
- , Viviane Tran
- & Jean-François Côté
-
Article
| Open AccessA biomaterial with a channel-like pore architecture induces endochondral healing of bone defects
A bioengineering approach to enhance the regeneration of large bone defects is lacking. Here, the authors show that a biomaterial scaffold with a channel-like pore architecture enables organized endochondral ossification through directional cell recruitment and extracellular matrix alignment.
- A. Petersen
- , A. Princ
- & G. N. Duda
-
Article
| Open AccessExpression-based drug screening of neural progenitor cells from individuals with schizophrenia
Unbiased large scale screening of small molecules for drug discovery in psychiatric disease is technically challenging and financially costly. Here, Readhead and colleagues integrate in silico and in vitro approaches to design and conduct transcriptomic drug screening in schizophrenia patient-derived neural cells, in order to survey novel pathologies and points of intervention.
- Benjamin Readhead
- , Brigham J. Hartley
- & Kristen J. Brennand
-
Article
| Open AccessA distinct isoform of ZNF207 controls self-renewal and pluripotency of human embryonic stem cells
Self-renewal and pluripotency of human embryonic stem cells (hESCs) depends upon the function of the transcription factor OCT4. Here, the authors identified proteins associated with the OCT4 enhancer, notably ZNF207 that maintains both pluripotency and differentiation towards ectoderm through isoform switching.
- Fang Fang
- , Ninuo Xia
- & Renee A. Reijo Pera
-
Article
| Open AccessTesticular endothelial cells are a critical population in the germline stem cell niche
Self-renewal of spermatogonial stem cells (SSC) is necessary for spermatogenesis and male fertility. Here the authors identify testicular endothelial cells (TECs) as a source of 5 key growth factors for self-renewal and expansion of human and mouse SSCs.
- Dong Ha Bhang
- , Bang-Jin Kim
- & Sandra Ryeom
-
Article
| Open AccessHSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons
The early molecular events that ultimately lead to neuronal cell death in pathologies such as Parkinson’s disease are poorly understood. Here the authors use pluripotent stem-cell-derived human midbrain neurons and chemical biology tools to gain molecular level insight into the events induced by toxic and genetic stresses that mimic those occurring during neurodegeneration.
- Sarah Kishinevsky
- , Tai Wang
- & Lorenz Studer
-
Article
| Open AccessLin−CCR2+ hematopoietic stem and progenitor cells overcome resistance to PD-1 blockade
Brain tumors are difficult to treat using existing immunotherapeutic strategies. Here, the authors show that in brain tumors resistant to PD-1 blockade, HSCs expressing CCR2+ can reverse treatment resistance and sensitizes mice to immunotherapy.
- Catherine T. Flores
- , Tyler J. Wildes
- & Duane A. Mitchell
-
Article
| Open AccessMulti-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors
Combining decellularised scaffolds with patient-derived cells holds promise for bioengineering of functional tissues. Here the authors develop a two-stage approach to engineer an oesophageal graft that retains the structural organisation of native oesophagus.
- Luca Urbani
- , Carlotta Camilli
- & Paolo De Coppi
-
Article
| Open AccessTracing the transitions from pluripotency to germ cell fate with CRISPR screening
Primordial Germ Cell-Like Cells (PGCLCs) are an in vitro model for primordial germ cell development. Here, the authors couple a novel compound reporter with CRISPR screening to identify key genes for exit from pluripotency and acquisition of PGCLC fate; specifically identifying Nr5a2 and Zfp296.
- Jamie A. Hackett
- , Yun Huang
- & M. Azim Surani
-
Article
| Open AccessDisrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa
Mutations in pre-mRNA processing factors cause autosomal dominant retinitis pigmentosa. Here the authors provide insights into the pathophysiological mechanisms underlying non-syndromic retinal disease caused by heterozygous mutations in genes encoding ubiquitously expressed splicing factors.
- Adriana Buskin
- , Lili Zhu
- & Majlinda Lako
-
Article
| Open AccessMicroglia innately develop within cerebral organoids
Brain organoid models reported to date lack cells of mesodermal origin, such as microglia. Here, the authors demonstrate that mature microglia-like cells are generated within their cerebral organoid model, providing new avenues for studying human microglia in a three-dimensional brain environment.
- Paul R. Ormel
- , Renata Vieira de Sá
- & R. Jeroen Pasterkamp
-
Article
| Open AccessEpigenomic map of human liver reveals principles of zonated morphogenic and metabolic control
Spatial mapping of genomic programs in tissue cells is an important step in the understanding of organ function and disease. Here, the authors provide a spatially resolved epigenomic and transcriptomic map of human liver and show porto-central gradients in metabolic and morphogen networks and transcription factor binding sites as a basis to better understand liver regeneration and function.
- Mario Brosch
- , Kathrin Kattler
- & Jochen Hampe
-
Article
| Open AccessNotch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma
Group 3 medulloblastoma is an aggressive pediatric brain tumour that disseminates through the leptomeningeal cerebral spinal fluid. Here, the authors show that in Group 3 medulloblastoma NOTCH1 activates BMI1 through the activation of TWIST1, driving metastasis and self-renewal, and in mouse models a NOTCH1 blocking antibody decreased spinal metastases.
- Suzana A. Kahn
- , Xin Wang
- & Samuel H. Cheshier
-
Article
| Open AccessMyelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors
Human blood cells all develop from haematopoietic stem cells (HSCs), classically thought to be multipotent. Here the authors show, using single-cell RNA-seq and functional assays, that loss of erythroid potential and commitment to the myelo-lymphoid lineage occurs within the purest HSC compartment to date.
- Serena Belluschi
- , Emily F. Calderbank
- & Elisa Laurenti
-
Article
| Open AccessDynamic intercellular transport modulates the spatial patterning of differentiation during early neural commitment
How heterogeneities arise in stem cell populations remains unclear. Here, Glen et al. find that in ESC colonies cell cycle asynchronies modulate gap junctions, causing variation in intracellular signalling molecule diffusion between cells, and ultimately in spatial heterogeneity in differentiation.
- Chad M. Glen
- , Todd C. McDevitt
- & Melissa L. Kemp
-
Article
| Open AccessBi-directional cell-pericellular matrix interactions direct stem cell fate
3D hydrogels have provided information on the physical requirements of stem cell fate, but the contribution of interactions with the pericellular environment are under-explored. Here the authors show that pericellular matrix secreted by human bone marrow stromal cells (hMSC) embedded in a HA-based hydrogel contribute to hMSC fate.
- Silvia A. Ferreira
- , Meghna S. Motwani
- & Eileen Gentleman
-
Article
| Open AccessA stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation
Induced neurons, but not induced pluripotent stem cell (iPSC)-derived neurons, preserve age-related traits. Here, the authors demonstrate that blood-derived induced neural stem cells (iNSCs), despite lacking a pluripotency transit, lose age-related signatures.
- Chao Sheng
- , Johannes Jungverdorben
- & Oliver Brüstle
-
Article
| Open AccessMolecular characterization and prospective isolation of human fetal cochlear hair cell progenitors
Hearing requires mechanosensitive hair cells in the organ of Corti, which derive from progenitors of the cochlear duct. Here the authors examine human inner ear development by studying key developmental markers and describe organoid cultures from human cochlear duct progenitors for in vitro hair cell differentiation.
- Marta Roccio
- , Michael Perny
- & Pascal Senn
-
Article
| Open AccessCell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
Ageing causes an inability to replace damaged tissue. Here, the authors perform proteomics analyses of human haematopoietic stem cells and other cells in the bone marrow niche at different ages and show changes in central carbon metabolism, reduced bone marrow niche function, and enhanced myeloid differentiation.
- Marco L. Hennrich
- , Natalie Romanov
- & Anthony D. Ho
-
Article
| Open AccessDamage-induced reactive oxygen species enable zebrafish tail regeneration by repositioning of Hedgehog expressing cells
Reactive oxygen species (ROS) are required to initiate regeneration but the mechanisms regulating its production are unclear. Here, the authors show in zebrafish larval tail regeneration that ROS is released by mobilised notochord cells enables their repositioning in the damage site, assisted by secreted Hh.
- Maria Montserrat Garcia Romero
- , Gareth McCathie
- & Henry Hamilton Roehl
-
Article
| Open AccessLnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia
Loss of Fancd2 leads to replication stress intolerance and Fanconi Anemia, where haematopoietic stem cell (HSC) function is compromised. Here, the authors show that Lnk/Sh2b3 loss restores HSC proliferation and survival in Fancd2 knockout mice and ameliorates replication stress in a cytokine/JAK2 signaling dependent manner.
- Joanna Balcerek
- , Jing Jiang
- & Wei Tong
-
Article
| Open AccessMed23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells
Hematopoietic stem cells (HSCs) in the bone marrow are quiescent, but are activated in response to stress. Here, the authors show that loss of Med23 leads to greater activation and enhanced myeloid potential of HSCs in response to stress, also Med23 maintains stemness gene expression and suppresses myeloid genes.
- Xufeng Chen
- , Jingyao Zhao
- & Xiaolong Liu
-
Article
| Open AccessRapid functional genetics of the oligodendrocyte lineage using pluripotent stem cells
The isolation and propagation of oligodendroglial cells from postnatal animals can be impractical for functional genetic studies. This study highlights the potential of a new approach to rapidly generate oligodendrocytes and their progenitors from mouse embryonic and induced pluripotent stem cells, independent of mouse strain or mutational status.
- Angela M. Lager
- , Olivia G. Corradin
- & Paul J. Tesar
-
Article
| Open AccessCharacterization and targeting of malignant stem cells in patients with advanced myelodysplastic syndromes
Myelodysplastic syndrome (MDS) arises from mutations in hematopoietic stem cells (HSCs). Here, the authors demonstrate that HSCs in higher-risk MDS express the surface marker CD123 and are characterized by activation of protein synthesis machinery and increased oxidative phosphorylation.
- Brett M. Stevens
- , Nabilah Khan
- & Craig T. Jordan
-
Article
| Open AccessConservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells
The Mll3/4 histone methyltransferases can act as tumour suppressors in humans. Here, the authors identify three orthologs of mammalian MLL3/4 in the planarian Schmidtea mediterranea and show that knockdown causes outgrowths in regenerating animals, suggesting that the tumour suppressive function of these genes is deeply conserved.
- Yuliana Mihaylova
- , Prasad Abnave
- & A. Aziz Aboobaker
-
Article
| Open AccessLinking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses
The functional significance of the observed heterogeneity of androgen receptor (AR) expression in prostate cancer is unknown. Here the authors show AR expression heterogeneity is associated with distinct castration/enzalutamide responses and identify BCL-2 as a potential therapeutic target in castration-resistant prostate cancer.
- Qiuhui Li
- , Qu Deng
- & Dean G. Tang
-
Article
| Open AccessAdipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
During mammary gland involution, the organ undergoes extensive remodeling. Here, the authors explore the role of mammary gland adipose tissue (mgWAT) in this process and demonstrate that adipocyte hypertrophy and lipid trafficking underlie mgWAT expansion and epithelial regression.
- Rachel K. Zwick
- , Michael C. Rudolph
- & Valerie Horsley
-
Article
| Open AccessRestricted cell cycle is essential for clonal evolution and therapeutic resistance of pre-leukemic stem cells
Cell cycle kinetics of pre-leukemic stem cells (pre-LSCs) may be an important determinant of clonal evolution and therapeutic resistance. Here, the AUs use a transgenic T-ALL mouse model that allows non-dividing cells to be tracked and identify a subset of non-dividing pre-LSCs maintained by p21.
- Cedric S. Tremblay
- , Jesslyn Saw
- & David J. Curtis
-
Article
| Open AccessJunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin
Epidermal homeostasis is maintained by the activity of stem cells. Here, the authors show that deficiency of the transcription factor JunB leads to altered Notch signaling in stem cells, resulting in a cell fate switch and de novo formation of aberrant sebaceous glands, altered epidermal differentiation and impaired barrier function.
- Karmveer Singh
- , Emanuela Camera
- & Karin Scharffetter-Kochanek
-
Article
| Open AccessPrecardiac organoids form two heart fields via Bmp/Wnt signaling
The heart arises from distinct progenitor cells of both the first and second heart fields (FHF and SHF). Here, the authors generated precardiac organoids from mouse and human pluripotent cells and show that FHF and SHF cells form similarly to their in vivo counterparts in response to BMP and Wnt signalling, respectively.
- Peter Andersen
- , Emmanouil Tampakakis
- & Chulan Kwon
-
Article
| Open AccessATP activates bestrophin ion channels through direct interaction
Human Bestrophin1 (hBest1), a calcium-activated chloride channel in retinal pigment epithelium (RPE), is essential for retina physiology. Using electrophysiological and structural approaches, the authors uncover an ATP-dependent activation mechanism of hBest1, and identify an ATP-binding motif.
- Yu Zhang
- , Alec Kittredge
- & Tingting Yang
-
Article
| Open AccessA metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways
HLX transcription factor regulates haematopoietic stem and progenitor cell (HSPC) differentiation and is overexpressed in acute myeloid leukemia. Here the authors show that HLX overexpression leads to myeloid differentiation block in zebrafish and human HSPCs by direct regulation of metabolic pathways.
- Indre Piragyte
- , Thomas Clapes
- & Eirini Trompouki
-
Article
| Open AccessInterleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids
Human pluripotent stem cell-derived intestinal organoids (hIOs) are a useful model with which to study intestinal development and disease, but they require in vivo maturation to resemble adult tissue. Here, the authors show that T lymphocyte-derived IL-2 induces hIO maturation in vitro through the activation of STAT3.
- Kwang Bo Jung
- , Hana Lee
- & Mi-Young Son
-
Article
| Open AccessGenetic dissection of clonal lineage relationships with hydroxytamoxifen liposomes
Targeted genetic dissection of tissues can be used to identify cell populations and lineages. Here the authors develop 4-hydroxytamoxifen liposomes for the localized induction of CreERT2.
- Ryan C. Ransom
- , Deshka S. Foster
- & Michael T. Longaker
Browse broader subjects
Browse narrower subjects
- Adult stem cells
- Ageing
- Cancer stem cells
- Embryonic germ cells
- Embryonic stem cells
- Epigenetic memory
- Haematopoietic stem cells
- Heart stem cells
- Intestinal stem cells
- Mammary stem cells
- Mesenchymal stem cells
- Multipotent stem cells
- Muscle stem cells
- Neural stem cells
- Pluripotent stem cells
- Quiescence
- Regeneration
- Reprogramming
- Self-renewal
- Skin stem cells
- Stem-cell differentiation
- Stem-cell niche
- Totipotent stem cells
- Transdifferentiation