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Cell Stem Cell
This journal offers authors two options (open access or subscription) to publish research

Aug 05, 2021

Volume 28Issue 8p1335-1500
Open Archive
On the cover: In this issue, Dray et al. (1457–1472), by combining long-term intravital imaging of neural stem cells with functional assays in vivo, mathematical modeling, and spatial statistics, show how local cell-cell interactions result in a spatiotemporal coordination of stem cell activation events. Here, the dancers are personifications of the neural stem cells that coordinate their movements in space and time, giving the impression of a choreographed ballet. Image courtesy of Charlene Letenneur....
On the cover: In this issue, Dray et al. (1457–1472), by combining long-term intravital imaging of neural stem cells with functional assays in vivo, mathematical modeling, and spatial statistics, show how local cell-cell interactions result in a spatiotemporal coordination of stem cell activation events. Here, the dancers are personifications of the neural stem cells that coordinate their movements in space and time, giving the impression of a choreographed ballet. Image courtesy of Charlene Letenneur.

Previews

  • Infection makes micro-CHIPs into macro-CHIPs

    • Jayakrishnan Gopakumar,
    • Siddhartha Jaiswal
    In this issue of Cell Stem Cell, Hormaechea-Agulla et al. (2021) demonstrate that IFNγ signaling following an infection in mice provides a selective pressure that drives growth of Dnmt3a−/− hematopoietic stem cells. This clonal expansion is mediated by global methylation changes that lead to an increased self-renewing capacity.
  • Cervical organoids go viral

    • Sara Sartini,
    • Alice Soragni
    In this issue of Cell Stem Cell, Lõhmussaar et al. (2021) describe a versatile platform for generating long-term patient-derived organoids from hysterectomies and Pap brush cells. They establish malignant and benign cervix tissue organoids from both endo- and ectocervix that have applications ranging from precision medicine to infection modeling.
  • Know thy neighbor: Modeling spatiotemporal cell-fate patterns in a neural stem cell niche

    • Michael Mattocks,
    • Vincent Tropepe
    How lineage and the microenvironment influence stem cell homeostasis at a population level remains unresolved. In this issue of Cell Stem Cell, Dray et al. (2021) use in vivo imaging and statistical modeling to discover a key role for local progenitor cell descendants in constraining neural stem cell divisions.
  • Race to the bottom: Darwinian competition in early intestinal tumorigenesis

    • Ramesh A. Shivdasani
    Mutant oncogenes could enable clonal dominance by cell-intrinsic means or by suppressing nearby wild-type stem cells. Reporting recently in Nature, three groups demonstrate potent neighborhood effects, both within intestinal crypts (Flanagan et al., 2021; van Neerven et al., 2021) and across crypts through intermediary sub-epithelial trophocytes (Yum et al., 2021).

Review

  • Stem cells and origins of cancer in the upper gastrointestinal tract

    • Yoku Hayakawa,
    • Hiroshi Nakagawa,
    • Anil K. Rustgi,
    • Jianwen Que,
    • Timothy C. Wang
    Rustgi, Que, and Wang discuss the biology of gastroesophageal stem cells and their role as the cell-of-origin in cancer. They summarize niche-stem cell interactions in metaplasia and early expansion of mutated stem-cell-derived clones during carcinogenesis. New approaches to study gastroesophageal stem cells and advance the field are also discussed.

Articles

  • Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly

    • Veronica Krenn,
    • Camilla Bosone,
    • Thomas R. Burkard,
    • Julia Spanier,
    • Ulrich Kalinke,
    • Arianna Calistri,
    • Cristiano Salata,
    • Raissa Rilo Christoff,
    • Patricia Pestana Garcez,
    • Ali Mirazimi,
    • Jürgen A. Knoblich
    Krenn et al. used human brain organoids to compare the effects of ZIKV and HSV-1 on brain development. They reveal that the two viruses impair organoid growth by inducing distinct morphological and transcriptional changes. Moreover, the specific defects caused by ZIKV and HSV-1 can be prevented by distinct interferons.
  • Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer

    • Kadi Lõhmussaar,
    • Rurika Oka,
    • Jose Espejo Valle-Inclan,
    • Milou H.H. Smits,
    • Hila Wardak,
    • Jeroen Korving,
    • Harry Begthel,
    • Natalie Proost,
    • Marieke van de Ven,
    • Onno W. Kranenburg,
    • Trudy G.N. Jonges,
    • Ronald P. Zweemer,
    • Sebastiaan Veersema,
    • Ruben van Boxtel,
    • Hans Clevers
    Human-based model systems that faithfully recapitulate cervical cancer and causative HPV infection are scarce and often inadequate. With the advances in organoid technology, Lõhmussaar et al. have now extended this knowledge to the cervix, describing a successful derivation of endo- and ectocervical organoids as well as tumoroids from the associated malignancies.
  • Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression

    • Daochun Sun,
    • Xuanhua P. Xie,
    • Xiyuan Zhang,
    • Zilai Wang,
    • Sameer Farouk Sait,
    • Swathi V. Iyer,
    • Yu-Jung Chen,
    • Rebecca Brown,
    • Dan R. Laks,
    • Mollie E. Chipman,
    • Jack F. Shern,
    • Luis F. Parada
    An embryonic neural crest Schwann cell lineage progenitor population initiates NF1-associated peripheral nerve tumors. Rare tumor cells with stem-like features are relatively quiescent yet mediate response to chemotherapy relapse and efficiently seed tumors in transplantation. Transcriptionally related cells were identified in a primary human NF1 tumor at the single-cell level. Transgenic mouse models demonstrate that targeting both CSCs and dividing tumor cells provides the best treatment outcomes.
  • Reactivation of the Hedgehog pathway in esophageal progenitors turns on an embryonic-like program to initiate columnar metaplasia

    • Alizée Vercauteren Drubbel,
    • Sheleya Pirard,
    • Simon Kin,
    • Benjamin Dassy,
    • Anne Lefort,
    • Frédérick Libert,
    • Sachiyo Nomura,
    • Benjamin Beck
    The Hedgehog pathway is activated in squamous progenitors from the foregut in a model of chronic reflux-induced columnar metaplasia. Activation of the Hedgehog pathway turns a subset of esophageal progenitors into columnar cells in a Sox9-dependent manner. This transcommitment involves a step of dedifferentiation into embryonic-like esophageal progenitors.
  • Chronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling

    • Daniel Hormaechea-Agulla,
    • Katie A. Matatall,
    • Duy T. Le,
    • Bailee Kain,
    • Xiaochen Long,
    • Pawel Kus,
    • Roman Jaksik,
    • Grant A. Challen,
    • Marek Kimmel,
    • Katherine Y. King
    Hormaechea-Agulla and colleagues demonstrate that chronic mycobacterial infection drives the expansion of hematopoietic stem cells deficient in Dnmt3a, the gene most commonly mutated in clonal hematopoiesis. Interferon gamma signaling is sufficient to promote Dnmt3a−/− clonal expansion, which is associated with broad changes in epigenetic regulation of a prodifferentiation gene program.
  • Featured Article
  • Transient suppression of transplanted spermatogonial stem cell differentiation restores fertility in mice

    • Yoshiaki Nakamura,
    • David J. Jörg,
    • Yayoi Kon,
    • Benjamin D. Simons,
    • Shosei Yoshida
    Nakamura et al. analyzed the fate of transplanted mouse spermatogonial stem cells (SSCs) at single-cell resolution. They found that only a small fraction of equipotent SSCs repopulate over the long term and demonstrated a strategy to restore host fertility by transient suppression of donor SSC differentiation using a chemical inhibitor.
  • Dynamic spatiotemporal coordination of neural stem cell fate decisions occurs through local feedback in the adult vertebrate brain

    • Nicolas Dray,
    • Laure Mancini,
    • Udi Binshtok,
    • Felix Cheysson,
    • Willy Supatto,
    • Pierre Mahou,
    • Sébastien Bedu,
    • Sara Ortica,
    • Emmanuel Than-Trong,
    • Monika Krecsmarik,
    • Sébastien Herbert,
    • Jean-Baptiste Masson,
    • Jean-Yves Tinevez,
    • Gabriel Lang,
    • Emmanuel Beaurepaire,
    • David Sprinzak,
    • Laure Bally-Cuif
    Using intravital imaging in the zebrafish adult pallium, Dray et al. analyze the endogenous spatiotemporal activation pattern of NSCs in relation with their neighbors. They demonstrate that transient inhibitory interactions involving NSCs and progenitors along lineage progression generate an intrinsic niche that coordinates NSC recruitment at large scale and long term.

Short article

Resource

  • Cascade diversification directs generation of neuronal diversity in the hypothalamus

    • Yu-Hong Zhang,
    • Mingrui Xu,
    • Xiang Shi,
    • Xue-Lian Sun,
    • Wenhui Mu,
    • Haoda Wu,
    • Jingjing Wang,
    • Si Li,
    • Pengfei Su,
    • Ling Gong,
    • Miao He,
    • Mingze Yao,
    • Qing-Feng Wu
    Zhang et al. combine single-cell transcriptomics with lineage tracing to map the developmental trajectory of the mouse hypothalamus. They find that multiple cell types along the hypothalamic lineage hierarchy enable neuronal multifurcation, revealing a cascade diversification strategy for generating extreme neuronal diversity.
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