Stem cells articles within Nature Communications

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  • Article
    | Open Access

    Regenerative tissue engineering with mesenchymal stem cells is hampered by bulk methods of assessing differentiation status and a general assumption that expression of individual markers of stem cell differentiation correlate with functional capacity. Here the authors debunk this assumption by applying single-cell techniques to disassociate aggrecan mRNA abundance and matrix deposition.

    • Allison J. Cote
    • , Claire M. McLeod
    •  & Robert L. Mauck

  • Article
    | Open Access

    Several studies have recently demonstrated the role of the MSI2 RNA binding protein in normal and malignant haematopoietc stem cells. In this study, the authors show that MSI2 is required for maintaining myelodysplastic syndrome stem cells in mice and that MSI2 expression predicts poor prognosis in patients affected by this disease.

    • James Taggart
    • , Tzu-Chieh Ho
    •  & Michael G. Kharas

  • Article
    | Open Access

    It is feared that reprogramming may introduce DNA mutations. Here Bhutani et al. take three different reprogramming methods and using comparative whole genome analyses do identify nucleotide variations that are different in reprogrammed cells from the original fibroblasts, but none convey oncogenic potential.

    • Kunal Bhutani
    • , Kristopher L. Nazor
    •  & Jeanne F. Loring

  • Article
    | Open Access

    In fast proliferating embryonic stem cells (ESC) the DNA damage response is activated by mechanisms that are as yet elusive. Here, Ahuja et al.link the DNA damage response to replication stress in mouse ESCs, caused by a short G1 phase, and propose fork remodelling as maintaining genome stability in embryos.

    • Akshay K. Ahuja
    • , Karolina Jodkowska
    •  & Massimo Lopes

  • Article
    | Open Access

    TLX is a nuclear receptor essential for neural stem cell self-renewal and recently involved in glioblastoma development. In this study, the authors show that inhibition of TLX expression, achieved using a dendrimer nanovector-delivered siRNAs or viral vector-delivered shRNAs, reduces glioblastoma stem cells self renewal and in vivotumour growth through activation of TET3.

    • Qi Cui
    • , Su Yang
    •  & Yanhong Shi

  • Article
    | Open Access

    The molecular mechanisms behind how autophagy may impact on developmental pathways and cell fate decisions are unclear. Here Wu et al.identify Notch receptors being taken up into ATG16L1-positive autophagosomes and, using a mouse mutant model, show that changes in autophagy can impact on stem cell fate.

    • Xiaoting Wu
    • , Angeleen Fleming
    •  & David C. Rubinsztein

  • Article
    | Open Access

    The suture mesenchyme has been postulated to act as the niche for stem cells for calvarial bones but the identity of the stem cells is unknown. Here, Maruyama et al.suggest that Axin2 expressing cells act as stem cells not only in craniofacial bone development and homeostasis but in injury-induced repair.

    • Takamitsu Maruyama
    • , Jaeim Jeong
    •  & Wei Hsu

  • Article
    | Open Access

    Drosophila neural stem cells (NSCs) are quiescent at early larval stages but how this is regulated is unclear. Here, Ding et al. show that quiescence of NSCs is mediated by cell-contact inhibition via the Hippo pathway transmembrane proteins Crumbs and Echinoid, which in turn are regulated by nutrient levels.

    • Rouven Ding
    • , Kevin Weynans
    •  & Christian Berger

  • Article
    | Open Access

    Stem cell competition mediates the balance between tissue homeostasis and tumour formation, but how this occurs is unclear. Here, Singh et al.show that the tumour suppressor Mlfl-adaptor molecule regulates the balance between germline stem cell and somatic cyst stem cell growth in the Drosophila testis niche.

    • Shree Ram Singh
    • , Ying Liu
    •  & Steven X. Hou

  • Article
    | Open Access

    Barrett’s oesophagus is a precancerous intestinal metaplasia that can progress to oesophageal adenocarcinoma. In this study, the authors isolate and characterize human Barrett’s stem cells and identify a specific genomic pedigree that supports the potential role of these cells as precursors of oesophageal adenocarcinoma.

    • Yusuke Yamamoto
    • , Xia Wang
    •  & Wa Xian

  • Article
    | Open Access

    The spatial location of proteins within a cell is a key element of protein function. Here the authors describe hyperLOPIT—a proteomics workflow that allows the simultaneous assignment of thousands of proteins to subcellular niches with high resolution—and apply it to mouse pluripotent stem cells.

    • Andy Christoforou
    • , Claire M. Mulvey
    •  & Kathryn S. Lilley

  • Article
    | Open Access

    Genetic and epigenetic abnormalities have been found to result from reprogramming of differentiated cells into human induced pluripotent stem cells (hiPSCs). Here, Klawitter et al.identify endogenous L1, Alu and SVA mobilization during reprogramming, highlighting the risk of insertional mutagens in hiPSCs.

    • Sabine Klawitter
    • , Nina V. Fuchs
    •  & Gerald G. Schumann

  • Article
    | Open Access

    There has been limited success in generating tissues from human induced pluripotent stem cells (hiPSCs). Here, the authors genetically engineer expression of the transcription factor Gata6 in a single isogenic hiPSC population resulting in complex tissue structures that exhibit liver bud-like properties.

    • Patrick Guye
    • , Mohammad R. Ebrahimkhani
    •  & Ron Weiss

  • Article
    | Open Access

    Intestinal homeostasis is ensured by stem cell self-renewal and differentiation while alterations of these processes can lead to cancer. In this study, using Drosophilagenetics the authors demonstrate that the loss of the transcription factor Sox21a blocks the differentiation of the intestinal stem cell progeny, which accumulate and form aggressive tumours.

    • Zongzhao Zhai
    • , Shu Kondo
    •  & Bruno Lemaitre

  • Article
    | Open Access

    The downstream effector of the Hippo pathway, YAP, is a critical regulator of both normal and cancer stem cell properties. In this study, the authors show that in basal-like breast tumors YAP forms a complex with SRF and together they induce a mammary stem cell gene signature through the transcriptional activation of IL-6.

    • Tackhoon Kim
    • , Suk-Jin Yang
    •  & Dae-Sik Lim

  • Article
    | Open Access

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders with diverse phenotypes and can derive from hematopietic stem cells after the acquisition of specific somatic aberrations. In this study, the authors show that MDS initiating cells in some cases of sideroblastic anemia with SF3B1 mutations, can arise from hematopoietic stem cells.

    • Syed A. Mian
    • , Kevin Rouault-Pierre
    •  & Ghulam J. Mufti

  • Article
    | Open Access

    MicroRNAs regulate haematopoietic stem cell (HSC) development to ensure the correct generation of blood cells. Haetscher et al. show in mice that miR-193b controls the life-long self-renewal ability of HSCs via AKT and STAT5 pathways, with loss of miR-193b accelerating HSC expansion and reducing differentiation.

    • Nadine Haetscher
    • , Yonatan Feuermann
    •  & Michael A. Rieger

  • Article
    | Open Access

    It is unclear why certain tissues are more susceptible to the consequences of aneuploidy. Here, in Drosophila, Gogendeau et al.identify aneuploidy as the cause of lengthened G1 and premature differentiation in both neural and adult intestinal stem cells, which prevents cells with abnormal genomes from cycling.

    • Delphine Gogendeau
    • , Katarzyna Siudeja
    •  & Renata Basto

  • Article
    | Open Access

    In vitro differentiation of human pluripotent stem cells (hPSCs) has enabled the generation of neuroectodermal tissues. Here, Sakaguchi et al.use a modified neocortical induction method to generate functional hippocampal granule and pyramidal-like neurons, as well as dorsomedial telencephalic tissues from hPSCs.

    • Hideya Sakaguchi
    • , Taisuke Kadoshima
    •  & Yoshiki Sasai

  • Article
    | Open Access

    The stem and progenitor populations that regulate mammary gland development are debated. Giraddi et al.use experimental and mathematical approaches to show that the three lineages of the mammary gland are maintained by their own restricted progenitors, and that cycling status links to the oestrus cycle.

    • Rajshekhar R. Giraddi
    • , Mona Shehata
    •  & John Stingl

  • Article
    | Open Access

    Generating organized kidney tissues from human pluripotent stem cell is a major challenge. Here, Freedman et al. describe a differentiation system forming spheroids and tubular structures, characteristic of these kidney structures, and using CRISPR/Cas9, delete PKD1/2, to model polycystic kidney disease.

    • Benjamin S. Freedman
    • , Craig R. Brooks
    •  & Joseph V. Bonventre

  • Article |

    How can you increase the success of hematopoietic stem cell (HSC) transplantation? In mice, Rolls et al. identify sleep in the donor as an important factor, finding that less sleep leads to 50% lower HSC engraftment, via miR-19b and suppressor of cytokine signaling genes, which prevent HSC homing.

    • Asya Rolls
    • , Wendy W. Pang
    •  & Luis de Lecea

  • Article
    | Open Access

    The physiological role of crosstalk between mesenchymal stem cells (MSC) and macrophages is unclear. Here, Phinney et al. show that MSCs transfer mitochondria to macrophages under oxidative stress, and desensitize macrophages to mitochondria by using microvesicles to repress Toll receptor signalling.

    • Donald G. Phinney
    • , Michelangelo Di Giuseppe
    •  & Luis A. Ortiz

  • Article
    | Open Access

    It is unclear how Notch1 signals regulate both the maintenance of the endothelial fate and the endothelial-to-hematopoietic transition in the embryonic aorta. Here the authors show that those cells in which Notch1 ligand Jag1 is out-competed by Dll4 remain endothelial, while higher Jag1 activity leads to generation of hematopoietic stem cells.

    • Leonor Gama-Norton
    • , Eva Ferrando
    •  & Anna Bigas

  • Article
    | Open Access

    Integrin-linked kinase (ILK) is known to modulate the extracellular matrix and hair follicle morphogenesis. Here, Morgner et al.show that lack of ILK causes an aberrant ratio of basement membrane laminins, activating stem cells and predisposing skin to carcinogenesis.

    • Jessica Morgner
    • , Sushmita Ghatak
    •  & Sara A. Wickström

  • Article
    | Open Access

    How bone morphogenetic proteins (BMPs) regulate haematopoietic stem cells (HSCs) later in development is unclear. Crisan et al.show that long-term repopulating HSCs in murine fetal liver and the bone marrow are of two types: either BMP activated or non-BMP activated, which correlate with different lineage outputs.

    • Mihaela Crisan
    • , Parham Solaimani Kartalaei
    •  & Elaine Dzierzak

  • Article |

    Changes in the metabolic state of stem cells can trigger a shift from quiescence into cell cycle entry. Here Maryanovichet al. identify mitochondrial carrier homolog 2 (MCH2) as a negative regulator of mitochondrial oxidative phosphorylation in haematopoietic stem cells, maintaining their homeostasis.

    • Maria Maryanovich
    • , Yehudit Zaltsman
    •  & Atan Gross

  • Article
    | Open Access

    The transcription factor estrogen-related receptor beta, Esrrb, regulates pluripotency genes in embryonic stem cells, but how it acts in trophoblast stem (TS) cells is unclear. Here, the authors identify Esrrb as a primary target of Fgf/Mek signaling and outline a unique TS cell-specific interactome to sustain stemness.

    • Paulina A. Latos
    • , Angela Goncalves
    •  & Myriam Hemberger

  • Article
    | Open Access

    The first haematopoietic stem and progenitor cells arise from the hemogenic endothelium of arterial vascular beds. Here the authors describe the mechanism that regulates the endothelial-to-haematopoietic transition and show that Sox17 and Notch1, genes critical to arterial endothelium identity, are also crucial repressors of haematopoietic fate.

    • Carlos O. Lizama
    • , John S. Hawkins
    •  & Ann C. Zovein

  • Article
    | Open Access

    Organogenesis is orchestrated by biochemical and biophysical stimuli. Here, Ma et al. generate a micro-patterned surface that provides mechanical cues which, when combined with biochemical signals, drive human pluripotent stem cells’ differentiation into beating cardiac microchambers resembling primitive hearts.

    • Zhen Ma
    • , Jason Wang
    •  & Kevin E. Healy

  • Article
    | Open Access

    Pseudogene derived long non-coding RNAs (lncRNAs) can regulate the expression of their ancestral genes. Here, the authors show that the Oct4 pseudogene OctP4lncRNA plays an important role in inducing and maintaining silencing of the ancestral Oct4 gene in differentiating mouse embryonic stem cells.

    • Michele Scarola
    • , Elisa Comisso
    •  & Roberta Benetti

  • Article
    | Open Access

    Reprogramming holds great promise for regenerative medicine but the molecular mechanisms governing the generation of induced pluripotent stem cells remain unclear. Here, the authors reveal functions for the axonal guidance cue Netrin-1 in constraining apoptosis at the early stage of reprogramming and in established pluripotent cells.

    • Duygu Ozmadenci
    • , Olivier Féraud
    •  & Fabrice Lavial

  • Article
    | Open Access

    Avoiding central cell necrosis at the centre of large engineered tissue constructs is an important issue forin vitrotissue engineering. Here, the authors demonstrate that this problem may be overcome by oxygenating human mesenchymal stem cells with artificial membrane-binding proteins.

    • James P. K. Armstrong
    • , Rameen Shakur
    •  & Anthony P. Hollander

  • Article
    | Open Access

    Characterizing the cellular stages that lead to induced reprogramming is of much interest and cell surface markers could offer unique advantages for this. Here the authors use surface proteomics and discover CD24 as a marker that tracks reprogramming-responsive cells and enables the analysis and enrichment of transgene-dependent and -independent induced pluriopotent stem cells.

    • Nika Shakiba
    • , Carl A. White
    •  & Peter W Zandstra

  • Article |

    Central to the lineage commitment of multipotent mesenchymal stem cells is the nuclear receptor PPARγ, the master regulator of adipogenesis. Here the authors use a variety of structural approaches to rationally design PPARγ inverse agonist SR2595, and demonstrate its ability to promote osteogenesis.

    • David P. Marciano
    • , Dana S. Kuruvilla
    •  & Patrick R. Griffin

  • Article
    | Open Access

    Skeletal muscle satellite cells are important for muscle regeneration, but their regulatory mechanisms are largely unknown. Here the authors identify arginine methyltransferase Prmt5 as a key regulator of satellite cell maintenance and function in adult mice, and show that Prmt5 acts mainly but not exclusively on the cell cycle inhibitor p21.

    • Ting Zhang
    • , Stefan Günther
    •  & Thomas Braun

  • Article |

    Chronic myeloid leukaemia is characterized by the genetic translocation t(9;22) encoding for BCR-ABL oncogene; however, the molecular mechanisms of disease progression are poorly understood. Here Amabile et al. show that aberrant methylation is promoted by BCR-ABL, driving the evolution of the disease.

    • Giovanni Amabile
    • , Annalisa Di Ruscio
    •  & Daniel G. Tenen

  • Article
    | Open Access

    The protein factors that bind to regulatory regions in the genome have not been systematically mapped. Here the authors performed chromatin immunoprecipitations for histone modifications associated with promoters, enhancers or heterochromatin in mouse embryonic stem cells and assigned a genome location to many factors important for pluripotency.

    • Erik Engelen
    • , Johannes H. Brandsma
    •  & Raymond A. Poot

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