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Stem Cells and Disease

Welcome to the Nature Communications Editors’ Highlights webpage on stem cells and disease. Each month our editors select a small number of Articles recently published in Nature Communications that they believe are particularly interesting or important.

The aim is to provide a snapshot of some of the most exciting work published in the area of stem cells and disease at Nature Communications. Each editor handles a different area of this research, as described below:

Ann Le Good handles manuscripts dealing with development and embryonic stem cells, including early pluripotency, cell fate decisions and regeneration.

Alfredo Sansone handles a range of cell biology methods manuscripts, including cell imaging, biosensors, organ-on-a-chip and microfluidic platforms.

Ylenia Lombardo handles manuscripts aimed at the identification and characterization of cancer stem cells from different type of tumors, their survival pathways and therapeutic strategies.

Robert Stephenson handles manuscripts dealing with stem cells; cell differentiation, tissue homeostasis and repair, reprogramming, therapy, development and disease modeling.

Ann Le Good

  • Nature Communications | Article | open

    The source of where definitive hematopoietic stem cells (dHSCs) develop in the mouse embyro has been much debated. Here, the authors identify that dHSCs arise from the intra-embyronic region by using murine embryonic explant transplantation but not from the yolk sac.

    • Miguel Ganuza
    • , Ashley Chabot
    • , Xing Tang
    • , Wenjian Bi
    • , Sivaraman Natarajan
    • , Robert Carter
    • , Charles Gawad
    • , Guolian Kang
    • , Yong Cheng
    •  &  Shannon McKinney-Freeman
  • Nature Communications | Article | open

    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
    • , Kimberly Johnson
    • , Rachelle Mariano
    • , Rachel Oshiro
    • , Alan Y. Wong
    • , Donald M. Bryant
    • , Bess M. Miller
    • , Alex Ratner
    • , Andy Chen
    • , William W. Ye
    • , Brian J. Haas
    •  &  Jessica L. Whited
  • Nature Communications | Article | open

    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
    • , Patrick Horn
    • , Samira Jaeger
    • , Volker Eckstein
    • , Violetta Steeples
    • , Fei Ye
    • , Ximing Ding
    • , Laura Poisa-Beiro
    • , Mang Ching Lai
    • , Benjamin Lang
    • , Jacqueline Boultwood
    • , Thomas Luft
    • , Judith B. Zaugg
    • , Andrea Pellagatti
    • , Peer Bork
    • , Patrick Aloy
    • , Anne-Claude Gavin
    •  &  Anthony D. Ho
  • Nature Communications | Article | open

    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
    • , Damian Kao
    • , Samantha Hughes
    • , Alvina Lai
    • , Farah Jaber-Hijazi
    • , Nobuyoshi Kosaka
    •  &  A. Aziz Aboobaker
  • Nature Communications | Article | open

    Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells in vertebrate embryo aortas. Here, the authors perform single-cell RNA-sequencing of cells isolated from embryonic mouse aortas to identify genes and transcription factor networks activated during the endothelial-to-haematopoietic switch.

    • Chloé S. Baron
    • , Lennart Kester
    • , Anna Klaus
    • , Jean-Charles Boisset
    • , Roshana Thambyrajah
    • , Laurent Yvernogeau
    • , Valérie Kouskoff
    • , Georges Lacaud
    • , Alexander van Oudenaarden
    •  &  Catherine Robin
  • Nature Communications | Article | open

    The Southern (SWR) and Northern (NWR) are two subspecies of the White Rhinoceros with the NWR being almost extinct. Here, using assisted reproduction technology, the authors produce and cryopreserve SWR purebred and NWR-SWR hybrid embryos developed to the blastocyst stage, and also generate embryonic stem cell lines, in an attempt to save genes of the NWR.

    • Thomas B. Hildebrandt
    • , Robert Hermes
    • , Silvia Colleoni
    • , Sebastian Diecke
    • , Susanne Holtze
    • , Marilyn B. Renfree
    • , Jan Stejskal
    • , Katsuhiko Hayashi
    • , Micha Drukker
    • , Pasqualino Loi
    • , Frank Göritz
    • , Giovanna Lazzari
    •  &  Cesare Galli

Ylenia Lombardo

  • Nature Communications | Article | open

    BCL9 and Pygo are components of Wnt enhanceosome, which facilitates β-catenin-dependent transcription. Here, the authors show that deletion of Bcl9 and Pygo suppresses tumorigenesis and extends disease free survival in two different colorectal cancer models, suggesting a strategy for drugging β-catenin signalling in this cancer.

    • Juliusz Mieszczanek
    • , Laurens M. van Tienen
    • , Ashraf E. K. Ibrahim
    • , Douglas J. Winton
    •  &  Mariann Bienz
  • Nature Communications | Article | open

    Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

    • David M. Gay
    • , Rachel A. Ridgway
    • , Miryam Müeller
    • , Michael C. Hodder
    • , Ann Hedley
    • , William Clark
    • , Joshua D. Leach
    • , Rene Jackstadt
    • , Colin Nixon
    • , David J. Huels
    • , Andrew D. Campbell
    • , Thomas G. Bird
    •  &  Owen J. Sansom
  • Nature Communications | Article | open

    Drug resistance is one of the major causes of cancer-related deaths. Here, the authors using single cell RNA-seq of oral squamous cell carcinoma patient samples pre- and post-cisplatin treatment show that phenotypically homogenous cell populations display cell state plasticity, with poised chromatin marks at mesenchymal genes in epithelial cells, and that the loss of stem factor Sox2 but gain of Sox9 expression (with de novo gain of H3K27ac sites) is associated with drug-induced adaptation.

    • Ankur Sharma
    • , Elaine Yiqun Cao
    • , Vibhor Kumar
    • , Xiaoqian Zhang
    • , Hui Sun Leong
    • , Angeline Mei Lin Wong
    • , Neeraja Ramakrishnan
    • , Muhammad Hakimullah
    • , Hui Min Vivian Teo
    • , Fui Teen Chong
    • , Shumei Chia
    • , Matan Thangavelu Thangavelu
    • , Xue Lin Kwang
    • , Ruta Gupta
    • , Jonathan R. Clark
    • , Giridharan Periyasamy
    • , N. Gopalakrishna Iyer
    •  &  Ramanuj DasGupta
  • Nature Communications | Article | open

    Bone marrow-derived epithelial cells can be recruited to sites of chronic inflammation. Here, the authors using allogenic bone marrow transplantation in a multistage murine cutaneous carcinogenesis model show that bone marrow-derived epithelial cells and hair follicle stem cells are recruited to cutaneous neoplasms during tumor promotion of carcinogen-exposed skin and bone marrow.

    • Heuijoon Park
    • , Sonali Lad
    • , Kelsey Boland
    • , Kelly Johnson
    • , Nyssa Readio
    • , Guangchun Jin
    • , Samuel Asfaha
    • , Kelly S. Patterson
    • , Ashok Singh
    • , Xiangdong Yang
    • , Douglas Londono
    • , Anupama Singh
    • , Carol Trempus
    • , Derek Gordon
    • , Timothy C. Wang
    •  &  Rebecca J. Morris
  • Nature Communications | Article | open

    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
    • , Jeffrey A. Drake
    • , Ginger L. Moore
    • , Bayli DiVita Dean
    • , Rebecca S. Abraham
    •  &  Duane A. Mitchell
  • Nature Communications | Article | open

    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
    • , Angelo D’Alessandro
    • , Travis Nemkov
    • , Amanda Winters
    • , Courtney L. Jones
    • , Wei Zhang
    • , Daniel A. Pollyea
    •  &  Craig T. Jordan

Alfredo Sansone

  • Nature Communications | Article | open

    Measuring growth factors in single cells at physiologically relevant stimulation doses is challenging. Here the authors use fluorescent quantum dots and calibrated three-dimensional deconvolution microscopy to digitally count growth factors in single cells and reveal stimulation distributions in cancer cells.

    • Phuong Le
    • , Sung Jun Lim
    • , Brian C. Baculis
    • , Hee Jung Chung
    • , Kristopher A. Kilian
    •  &  Andrew M. Smith
  • Nature Communications | Article | open

    Single-cell detection methods are limited by the trade-off between flow rate and measurement precision. Here the authors introduce active loading, an optically triggered microfluidic system to concentrate diluted cell samples, which reduces clogging and decreases processing time in single-cell assays.

    • Nicholas L. Calistri
    • , Robert J. Kimmerling
    • , Seth W. Malinowski
    • , Mehdi Touat
    • , Mark M. Stevens
    • , Selim Olcum
    • , Keith L. Ligon
    •  &  Scott R. Manalis
  • Nature Communications | Article | open

    Therapeutic alteration of protein expression using modified mRNA is limited by immunogenicity and instability in vivo. Here the authors use antibody-coated lipid nanoparticles to deliver mRNA to leukocytes and drive expression of anti-inflammatory cytokines in an inflammatory bowel disease mouse model.

    • Nuphar Veiga
    • , Meir Goldsmith
    • , Yasmin Granot
    • , Daniel Rosenblum
    • , Niels Dammes
    • , Ranit Kedmi
    • , Srinivas Ramishetti
    •  &  Dan Peer
  • Nature Communications | Article | open

    Diagnostic tests need optimization to avoid invasive and costly repeated biopsies. Here the authors present an antibody-DNA barcoding approach where harvested single cells can be re-stained through custom oligonucleotide-fluorophore conjugates, enabling multiplexed analysis of cancer pathways.

    • Randy J. Giedt
    • , Divya Pathania
    • , Jonathan C. T. Carlson
    • , Philip J. McFarland
    • , Andres Fernandez del Castillo
    • , Dejan Juric
    •  &  Ralph Weissleder
  • Nature Communications | Article | open

    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
    • , Aida Moreno-Moral
    • , Li Yen Chong
    • , Po Yin Tang
    • , Nathan Peter Harmston
    • , Zuhua Cai
    • , Enrico Petretto
    • , Bien Keem Tan
    •  &  Karl Tryggvason
  • Nature Communications | Article | open

    Autophagic clearance of aggregates, aggrephagy, is essential for cellular homeostasis but tools to induce and monitor it are limited. Here the authors present a fluorescence-based aggrephagy induction assay to study spatiotemporal dynamics and control mechanisms driving protein aggregate clearance.

    • Anne F. J. Janssen
    • , Eugene A. Katrukha
    • , Wendy van Straaten
    • , Pauline Verlhac
    • , Fulvio Reggiori
    •  &  Lukas C. Kapitein

Robert Stephenson

  • Nature Communications | Article | open

    High fat diets (HFD) are thought to perturb murine hematopoiesis as a result of obesity. Here the authors find that short-term HFD reduces hematopoietic stem cells (HSC), disrupts lipid rafts and TGF-β1 signalling. Injecting HFD-fed mice with recombinant TGF-β1 can rescue HSC loss.

    • François Hermetet
    • , Anne Buffière
    • , Aziza Aznague
    • , Jean-Paul Pais de Barros
    • , Jean-Noël Bastie
    • , Laurent Delva
    •  &  Ronan Quéré
  • Nature Communications | Article | open

    Lineage segregation from conception to gastrulation has been mapped at the single cell level in mouse, human and monkey. Here, the authors provide a comprehensive analysis of porcine preimplantation development using single cell RNA-seq; mapping metabolic changes, X chromosome inactivation and signalling pathways.

    • Priscila Ramos-Ibeas
    • , Fei Sang
    • , Qifan Zhu
    • , Walfred W. C. Tang
    • , Sarah Withey
    • , Doris Klisch
    • , Liam Wood
    • , Matt Loose
    • , M. Azim Surani
    •  &  Ramiro Alberio
  • Nature Communications | Article | open

    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
    • , Yehudit Zaltsman
    • , Dilshad H. Khan
    • , Coral Halperin
    • , Emmanuel Amzallag
    • , Vladislav Krupalnik
    • , Michael Mullokandov
    • , Alon Silberman
    • , Ayelet Erez
    • , Aaron D. Schimmer
    • , Jacob H. Hanna
    •  &  Atan Gross
  • Nature Communications | Article | open

    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
    • , Chi Nok Chong
    • , Lei Tan
    • , Sadaf Amin
    • , Zohreh Sadat Badieyan
    • , Suranjit Mukherjee
    • , Zaniar Ghazizadeh
    • , Hui Zeng
    • , Min Guo
    • , Miguel Crespo
    • , Tuo Zhang
    • , Reyn Kenyon
    • , Christopher L. Robinson
    • , Effie Apostolou
    • , Hui Wang
    • , Jenny Zhaoying Xiang
    • , Todd Evans
    • , Lorenz Studer
    •  &  Shuibing Chen
  • Nature Communications | Article | open

    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
    • , Yang Li
    • , Qinqin Jiang
    • , Nicholas Holdreith
    • , Brijendra Singh
    • , Vemika Chandra
    • , Kaosheng Lv
    • , Jian-gang Ren
    • , Krasimira Rozenova
    • , Weihua Li
    • , Roger A. Greenberg
    •  &  Wei Tong
  • Nature Communications | Article | open

    Functional salivary glands have not been generated from embryonic stem cells (mESCs) to date. Here the authors demonstrate directed in vitro differentiation of mESCs to oral ectoderm and salivary gland rudiments that form mature, functional salivary glands after orthotopic transplantation.

    • Junichi Tanaka
    • , Miho Ogawa
    • , Hironori Hojo
    • , Yusuke Kawashima
    • , Yo Mabuchi
    • , Kenji Hata
    • , Shiro Nakamura
    • , Rika Yasuhara
    • , Koki Takamatsu
    • , Tarou Irié
    • , Toshiyuki Fukada
    • , Takayoshi Sakai
    • , Tomio Inoue
    • , Riko Nishimura
    • , Osamu Ohara
    • , Ichiro Saito
    • , Shinsuke Ohba
    • , Takashi Tsuji
    •  &  Kenji Mishima