Featured
-
-
Article
| Open AccessCore transcription regulatory circuitry orchestrates corneal epithelial homeostasis
Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.
- Mingsen Li
- , Huaxing Huang
- & Hong Ouyang
-
Article
| Open AccessPrime editing for functional repair in patient-derived disease models
Prime editing uses Cas9 nickase fused to a reverse transcriptase to edit genetic information. Here, the authors prime edit primary adult stem cells in 3D organoid cultures to show functional correction of pathogenic mutations without genome-wide off-target effects.
- Imre F. Schene
- , Indi P. Joore
- & Sabine A. Fuchs
-
Article
| Open AccessDental cell type atlas reveals stem and differentiated cell types in mouse and human teeth
Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.
- Jan Krivanek
- , Ruslan A. Soldatov
- & Igor Adameyko
-
Article
| Open AccessIL-33-ST2 axis regulates myeloid cell differentiation and activation enabling effective club cell regeneration
Signaling of IL-33 via its receptor, ST2, has been implicated in macrophage function in tissue repair. Here the authors show, using genetic mouse models and single-cell transcriptomic data, that the IL-33/ST2 axis regulates both ILC2-derived IL-13 and macrophage differentiation/reparative function required for club cell regeneration.
- Rania Dagher
- , Alan M. Copenhaver
- & Marina Pretolani
-
Article
| Open AccessHuman beige adipocytes for drug discovery and cell therapy in metabolic diseases
Methods to generate beige adipocytes from a human cell source are inefficient. Here, the authors present a protocol that efficiently generates beige adipocytes from human adipose-derived stem cells (ADSCs), which have potential utility in therapeutic development relating to metabolic diseases such as type 2 diabetes.
- Amar M. Singh
- , Liang Zhang
- & Stephen Dalton
-
Article
| Open AccessLong noncoding RNA SAM promotes myoblast proliferation through stabilizing Sugt1 and facilitating kinetochore assembly
Long noncoding RNA SAM (Sugt1 associated muscle) is upregulated in the proliferating myoblast cells. Here the authors investigate SAM knockout mice and suggest that SAM binds and stabilizes Sugt1, a co-chaperone protein that regulates kinetochore assembly.
- Yuying Li
- , Jie Yuan
- & Huating Wang
-
Article
| Open AccessThe mutational impact of culturing human pluripotent and adult stem cells
Genetic changes acquired during in vitro culture pose a challenge to application of stem cells. Here the authors use whole genome sequencing to show that cultured human adult and pluripotent stem cells have a high mutational load caused by oxidative stress and reduced oxygen tension in culture lowers mutation rates.
- Ewart Kuijk
- , Myrthe Jager
- & Edwin Cuppen
-
Article
| Open AccessYAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity
Hippo TEAD-transcriptional regulators YAP1 and TAZ modulate cell growth, but the downstream networks are unclear. Here, the authors use a genetically-encoded inhibitor of YAP1/TAZ interaction with TEAD (TEADi) to disrupt transcriptional networks for cell cycle and terminal differentiation in human keratinocytes and mouse skin.
- Yao Yuan
- , Jeannie Park
- & Ramiro Iglesias-Bartolome
-
Article
| Open AccessAn organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity
Pre-clinical cell culture models capturing the heterogeneity of childhood kidney tumours are limited. Here, the authors establish and characterise an organoid biobank of tumour and matched normal organoid cultures from over 50 children with different subtypes of kidney cancer.
- Camilla Calandrini
- , Frans Schutgens
- & Jarno Drost
-
Article
| Open AccessKlf5 acetylation regulates luminal differentiation of basal progenitors in prostate development and regeneration
The role of the Klf5 in early and postnatal prostate development and in regeneration is unclear. Here, the authors show that Klf5 acetylation regulates and maintains luminal differentiation of prostate basal progenitors and is essential following androgen-induced regeneration.
- Baotong Zhang
- , Xinpei Ci
- & Jin-Tang Dong
-
Article
| Open AccessIdentification of a Zeb1 expressing basal stem cell subpopulation in the prostate
Heterogeneous populations of basal cells in the prostate epithelium contain stem cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem cells that self-renew, generate prostate glandular structures with all 3 epithelial cell types and are required for prostate basal cell development.
- Xue Wang
- , Haibo Xu
- & Helen He Zhu
-
Article
| Open AccessGastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5−CD44+ cells
Cancers arising from the gastric squamous-columnar junction have high incidence and are characterized by a poor prognosis. Here, the authors use genetic mouse models to show that loss of p53 and Rb1 expression results in preferential tumour development at the gastric squamous-columnar junction that contains a large pool of osteopontin responsive Lgr5-CD44+ cells.
- Dah-Jiun Fu
- , Lianghai Wang
- & Alexander Yu. Nikitin
-
Article
| Open AccessExtracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture
Organoid cultures have been developed from multiple tissues, opening new possibilities for regenerative medicine. Here the authors demonstrate the derivation of GMP-compliant hydrogels from decellularized porcine small intestine which support formation and growth of human gastric, liver, pancreatic and small intestinal organoids.
- Giovanni Giuseppe Giobbe
- , Claire Crowley
- & Paolo De Coppi
-
Article
| Open AccessProcr-expressing progenitor cells are responsible for murine ovulatory rupture repair of ovarian surface epithelium
The ovary is covered by a surface epithelium (OSE) and cells mediating its repair post ovulation are unclear. Here, the authors identify the Protein C Receptor (Procr) as marking progenitor cells, distinct from Lgr5+ stem cells, on the murine surface epithelium that repair the OSE post ovulation.
- Jingqiang Wang
- , Daisong Wang
- & Yi Arial Zeng
-
Article
| Open AccessDamage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut
Epithelia are exposed to diverse types of environmental stress, but the mechanisms by which epithelial cells sense stress are not well understood. Here, the authors show that a Nox-ROS-Ask1-MKK3-p38 signaling axis integrates various types of stress to promote intestinal regeneration.
- Parthive H. Patel
- , Clothilde Pénalva
- & Bruce A. Edgar
-
Article
| Open AccessPriming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy
Hair follicles (HFs) are sensitive to chemotherapy but recover from quiescent HF stem cells, although sometimes chemotherapy results in permanent loss. Here, Kim et al. establish a model of permanent chemotherapy-induced alopecia to uncover the underlying mechanisms depleting human HF stem cells.
- Jin Yong Kim
- , Jungyoon Ohn
- & Ohsang Kwon
-
Article
| Open AccessTransit amplifying cells coordinate mouse incisor mesenchymal stem cell activation
Mouse incisor growth depends upon mesenchymal stromal cells (MSCs) and transit amplifying cells (TACs). Here the authors describe a distinct population of MSCs that is maintained by TACs through Dlk1 ligand and that contribute to MTACs and mesenchymal lineages including dental pulp and odontoblasts.
- Jemma Victoria Walker
- , Heng Zhuang
- & Bing Hu
-
Article
| Open AccessAWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis
Regeneration after injury in the Drosophila intestine involves early activation of intestinal stem cells (ISCs) and subsequent return to quiescence. Here the authors show that return to quiescence by ISCs involves BMP Type I receptor Tkv protein stabilization along with AWD mediated internalization into endocytic vesicles.
- Xiaoyu Tracy Cai
- , Hongjie Li
- & Heinrich Jasper
-
Article
| Open AccessAdult stem cell deficits drive Slc29a3 disorders in mice
Mutations in equilibrative nucleoside transporter 3 (ENT3), encoded by SLC29A3, cause a spectrum of human genetic disorders. Here, the authors show altered haematopoietic stem cell and mesenchymal stem cell fates in ENT3-deficient mice, due to misregulation of the AMPK-mTOR-ULK axis.
- Sreenath Nair
- , Anne M. Strohecker
- & Rajgopal Govindarajan
-
Article
| Open AccessDevelopmental kinetics and transcriptome dynamics of stem cell specification in the spermatogenic lineage
In neonatal testes, prospermatogonia generate both spermatogonia for the first wave of spermatogenesis and spermatogonial stem cells (SSCs) for maintenance of spermatogenesis in males. Here the authors characterize the development of mouse SSCs from prospermatogonia using single-cell RNA-seq and transplantation assays.
- Nathan C. Law
- , Melissa J. Oatley
- & Jon M. Oatley
-
Article
| Open AccessLoss of 5-methylcytosine alters the biogenesis of vault-derived small RNAs to coordinate epidermal differentiation
RNA modifications, including 5-methylcytosines, are known regulators of RNA metabolism affecting protein-RNA binding. Here, the authors reveal the role of m5C in the biogenesis of the non-coding vault-derived small RNAs.
- Abdulrahim A. Sajini
- , Nila Roy Choudhury
- & Michaela Frye
-
Article
| Open AccessDDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia
Sustained sperm production is dependent on activity of undifferentiated spermatogonia. Here, the authors demonstrate an essential role for RNA helicase DDX5 in maintenance of spermatogonia in adults through control of gene transcription plus RNA processing and export.
- Julien M. D. Legrand
- , Ai-Leen Chan
- & Robin M. Hobbs
-
Article
| Open AccessLoss of a proteostatic checkpoint in intestinal stem cells contributes to age-related epithelial dysfunction
Protein homeostasis maintenance (proteostasis) is critical for cell function, but declines during aging. Here the authors detail a proteostatic checkpoint in Drosophila intestinal stem cells coordinating cell cycle arrest with protein aggregate clearance, along with its role in aging related intestinal dysfunction.
- Imilce A. Rodriguez-Fernandez
- , Yanyan Qi
- & Heinrich Jasper
-
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 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 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 AccessIdentification of dynamic undifferentiated cell states within the male germline
Sustained spermatogenesis depends on stem cell activity which is contained within a population of undifferentiated spermatogonia. Here, the authors identify a new population of undifferentiated spermatogonia in adult testis that expresses the transcription factor PDX1 and has stem cell capacity.
- Hue M. La
- , Juho-Antti Mäkelä
- & Robin M. Hobbs
-
Article
| Open AccessHematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice
Dependence of hematopoietic stem cell (HSC) fate on the phase of the cell cycle has not been demonstrated in vivo. Here, the authors find that HSCs can differentiate into a downstream progenitor without physical division, even before progressing into the S phase of the cell cycle.
- Tatyana Grinenko
- , Anne Eugster
- & Ben Wielockx
-
Article
| Open AccessWnt ligands influence tumour initiation by controlling the number of intestinal stem cells
Wnt ligands are essential for intestinal homoeostasis and stem cell maintenance. Here, the authors show that reduction in Wnt secretion reduces the number of intestinal stem cells; this results in rapid fixation of mutated stem cells and accelerated adenoma formation due to lack of cell competition.
- D. J. Huels
- , L. Bruens
- & O. J. Sansom
-
Article
| Open AccessBasal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal
Extracellular matrix (ECM) remodelling is thought to have effects on muscle stem cells that support muscle homeostasis. Here the authors show ECM remodeling controls satellite cell self-renewal through deposition of laminin-α1 into the satellite cell niche.
- Shantisree Sandeepani Rayagiri
- , Daniele Ranaldi
- & Anne-Gaëlle Borycki
-
Article
| Open AccessSomatic mutagenesis in satellite cells associates with human skeletal muscle aging
Aging skeletal muscle shows declining numbers and activity of satellite cells. Here, Franco et al. show that in satellite cells of the human leg muscle vastus lateralis, somatic mutations accumulate with age and that these mutations become enriched in exons and promoters of genes involved in muscle function.
- Irene Franco
- , Anna Johansson
- & Maria Eriksson
-
Article
| Open AccessPeriosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin
The periosteum, a tissue lining the bone surface, and the bone marrow are known to contain bone-forming cells. Here the authors show that skeletal stem cells reside in the mouse periosteum, and that periosteal cells have common embryonic origins with bone marrow stromal/stem cells (BMSCs), but are better at bone repair and long-term integration than BMSCs.
- Oriane Duchamp de Lageneste
- , Anaïs Julien
- & Céline Colnot
-
Article
| Open AccessCombinatorial hydrogels with biochemical gradients for screening 3D cellular microenvironments
Tools to investigate a wide range of 3D microenvironmental parameters are important for understanding and controlling cell fate. Here, the authors develop hydrogels with orthogonal biochemical gradients and use this screening system to identify microenvironments that induce mesenchymal stem cell chondrogenesis.
- Sebastián L. Vega
- , Mi Y. Kwon
- & Jason A. Burdick
-
Article
| Open AccessLsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells
Satellite cells can differentiate both into myocytes and brown adipocytes. Here, the authors show that the histone demethylase Lsd1 prevents adipogenic differentiation of satellite cells by repressing expression of Glis1, and that its ablation changes satellite cell fate towards brown adipocytes and delays muscle regeneration in mice.
- Milica Tosic
- , Anita Allen
- & Roland Schüle
-
Article
| Open AccessLong-lived unipotent Blimp1-positive luminal stem cells drive mammary gland organogenesis throughout adult life
The role of stem/progenitor cell populations in mammary gland morphogenesis is not well understood. Here, the authors show that a transcriptional repressor, Blimp1, is expressed in a rare luminal stem cell population, which contribute to duct formation, and survive multiple rounds of pregnancy and involution.
- Salah Elias
- , Marc A. Morgan
- & Elizabeth J. Robertson
-
Article
| Open AccessQuantitative microscopy of the Drosophila ovary shows multiple niche signals specify progenitor cell fate
In the Drosophila ovary, it is unclear how signalling from the stem cell niche regulates follicle precursor cell fate/differentiation. Here, the authors use quantitative microscopy to define the role of Wnt, Hedgehog and Notch signalling in progenitor cells, showing regulation of cell fate and differentiation.
- Wei Dai
- , Amy Peterson
- & Denise J. Montell
-
Article
| Open AccessHGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5+ liver stem cells
Organ regeneration by transplantation of ESC/iPSC-derived tissues is a promising but still challenging approach. Here Lin et al. show that liver damage caused by a chemical insult induces not only fibrosis but also Lgr5+ cell expansion that can be further promoted by treatment with HGF/R-spondin1.
- Yuan Lin
- , Zhe-Ping Fang
- & Wei-Jie Zhou
-
Article
| Open AccessmiR-9a modulates maintenance and ageing of Drosophila germline stem cells by limiting N-cadherin expression
In the Drosophila testis, ageing leads to loss of germline stem cells. Here, the authors show that, during ageing in Drosophila, miR-9a is upregulated in male germline stem cells and regulates their proliferation by targeting N-cadherin.
- Yehonatan Epstein
- , Noam Perry
- & Hila Toledano
-
Article
| Open AccessTbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration
The abdominal skin expands rapidly during pregnancy. Here the authors show that a population of highly proliferative stem cell progenies expressing the transcription factor Tbx3 is required for abdominal skin expansion in pregnant mice.
- Ryo Ichijo
- , Hiroki Kobayashi
- & Fumiko Toyoshima
-
Article
| Open AccessWNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation
Human WNT10A mutations are associated with dental defects and adult onset ectodermal dysplasia. Xuet al. show that WNT10A-activated ß-catenin plays dual roles in adult epithelial progenitor proliferation and differentiation by complexing with KLF4 in differentiating, but not proliferating, cells.
- Mingang Xu
- , Jeremy Horrell
- & Sarah E. Millar
-
Article
| Open AccessHMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche
The function of high mobility group A1 (Hmga1) chromatin remodelling proteins in intestinal stem cells (ISC) is unknown. Here, the authors show that Hmga1 amplifies Wnt/β-catenin signalling to enhance self-renewal and inducesSox9to expand the Paneth cell compartment and enrich the ISC niche.
- Lingling Xian
- , Dan Georgess
- & Linda M. S. Resar
-
Article
| Open AccessA genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells
Individual human epidermal cells differ in their self-renewal ability. Here the authors perform genome-wide pooled RNAi screens to uncover the molecular basis for this heterogeneity, and identify genes conferring a clonal growth advantage on normal and neoplastic human epidermal cells.
- Gernot Walko
- , Samuel Woodhouse
- & Fiona M. Watt
-
Article
| Open AccessLipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells
There are two technical impediments for using purified Wnt proteins in serum-free stem cell cultures: rapid loss of activity and toxicity of detergents to stem cell self-renewal. Here, the authors show that lipid-stabilized Wnt3a can establish long-term culture of human intestinal and liver organoids.
- Nesrin Tüysüz
- , Louis van Bloois
- & Derk ten Berge
-
Article
| Open AccessClonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate
Age-associated decline in tissue function has been linked to alterations in adult stem cells, with implications for organ homeostasis and cellular therapy. Here, the authors study the heterogeneity of ageing mouse haematopoietic stem cells (HSCs) and find that the compromised blood cell-forming potential of individual and functionally defined aged HSCs can be reset by reprogramming.
- Martin Wahlestedt
- , Eva Erlandsson
- & David Bryder
-
Article
| Open AccessPten is necessary for the quiescence and maintenance of adult muscle stem cells
Pten is known to regulate haematopoietic stem cell functions. Here the authors show that Ptenalteration of Notch signalling has stage-specific muscle regenerative functions in muscle stem cells by preventing premature differentiation of quiescent cells and enhancing the self-renewal of activated cells.
- Feng Yue
- , Pengpeng Bi
- & Shihuan Kuang
-
Article
| Open AccessREST regulation of gene networks in adult neural stem cells
The transcription factor REST plays a crucial role in maintaining the adult neural stem cell pool. To better understand how REST maintains quiescence in neural progenitors, the authors use ChIP-seq and RNA-seq and find that REST regulates represses ribosome biogenesis, cell cycle and neuronal genes.
- Shradha Mukherjee
- , Rebecca Brulet
- & Jenny Hsieh
-
Article
| Open AccessSingle-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny
The identity and origin of adult mammary stem cells has been much debated. Here, the authors use a stochastic genetic labelling approach, together with optical tissue clearing, to visualize clonal progeny and show that unipotent stem/progenitor cells contribute to adult mammary gland development.
- Felicity M. Davis
- , Bethan Lloyd-Lewis
- & Christine J. Watson
-
Article
| Open AccessSelf-organized centripetal movement of corneal epithelium in the absence of external cues
The cornea is formed of cells that originate from the outer circle of stem cells and that move towards its centre. Here, the authors show that the movement pattern is self-organised, requiring no cues, and that stem cell leakage may account for the presence of stem cells at the centre of the cornea.
- Erwin P. Lobo
- , Naomi C. Delic
- & J. Guy Lyons
-
Article
| Open AccessInductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells
It is unclear how the microenvironment of the aorta-gonad-mesonephros influences haematopoietic stem cell (HSC) production early in mouse development. Here, Souilhol et al. use an in vitroaggregate system as a tool to understand how several pathways, BMP, SCF and Shh, may regulate HSC production.
- Céline Souilhol
- , Christèle Gonneau
- & Alexander Medvinsky