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

Aug 06, 2015

Volume 17Issue 2p127-248
Open Archive
On the cover: In this issue, Li et al. (195–203) show that mouse fibroblasts can be directly reprogrammed into neuronal cells with only a small-molecule cocktail, and in a related study, Hu et al. (204–212) describe similar findings in human cells. The cover art depicts the main stages of fibroblast to neuron conversion after small-molecule compound treatment. The concept was developed by Xiang Li, Yang Zhao, and Xiaohan Zuo, and the image was designed by Chuang Zhao....
On the cover: In this issue, Li et al. (195–203) show that mouse fibroblasts can be directly reprogrammed into neuronal cells with only a small-molecule cocktail, and in a related study, Hu et al. (204–212) describe similar findings in human cells. The cover art depicts the main stages of fibroblast to neuron conversion after small-molecule compound treatment. The concept was developed by Xiang Li, Yang Zhao, and Xiaohan Zuo, and the image was designed by Chuang Zhao.

In This Issue

Previews

  • Small Molecules Take a Big Step by Converting Fibroblasts into Neurons

    • Kimberley Babos,
    • Justin K. Ichida
    Direct lineage conversion could provide a rich source of somatic cell types for translational medicine, but concerns over the use of transgenic reprogramming factors have limited its potential. In this issue of Cell Stem Cell, Li et al. (2015) and Hu et al. (2015) identify small-molecule cocktails that can convert fibroblasts into functional neurons without exogenous genetic factors.
  • Resistance in the Ribosome: RUNX1, pre-LSCs, and HSPCs

    • Kyoko Ito,
    • Keisuke Ito
    Therapeutic targeting of pre-leukemic stem cells (pre-LSCs) may be a viable strategy to eradicate residual disease and prevent leukemia relapse. Now in Cell Stem Cell, Cai et al. (2015) show that loss-of-function mutations in RUNX1 reduce ribosome biogenesis and provide pre-LSCs a selective advantage over normal hematopoietic cells through increased stress resistance.
  • Cell Cycle Rules Pluripotency

    • Ludovic Vallier
    Stem cell self-renewal is intrinsically associated with cell cycle control. However, the precise mechanisms coordinating cell fate choices and cell cycle remain to be fully uncovered. Now in Cell, Gonzales et al. (2015) and colleagues demonstrate that factors controlling the G2/M phase are necessary to block pluripotency upon induction of differentiation.
  • MT-Nanotubes: Lifelines for Stem Cells

    • Marc Amoyel,
    • Erika A. Bach
    Niche cells produce secreted factors that promote the self-renewal of stem cells in their immediate proximity, but how signaling is restricted to stem cells is not well understood. Inaba et al. (2015) report that microtubule (MT) structures called MT-nanotubes control activation of the primary self-renewal pathway in Drosophila testes.

Forum

  • Patient-Funded Trials: Opportunity or Liability?

    • Danielle Marie Wenner,
    • Jonathan Kimmelman,
    • Alex John London
    Patient-funded trials (PFTs) are gaining traction as a means of accelerating clinical translation. However, such trials sidestep mechanisms that promote rigor, relevance, efficiency, and fairness. We recommend that funding bodies or research institutions establish mechanisms for merit review of patient-funded trials, and we offer some basic criteria for evaluating PFT protocols.

Articles

  • dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration

    • Amanda M. Nelson,
    • Sashank K. Reddy,
    • Tabetha S. Ratliff,
    • M. Zulfiquer Hossain,
    • Adiya S. Katseff,
    • Amadeus S. Zhu,
    • Emily Chang,
    • Sydney R. Resnik,
    • Carly Page,
    • Dongwon Kim,
    • Alexander J. Whittam,
    • Lloyd S. Miller,
    • Luis A. Garza
    Wound-induced hair neogenesis provides a model for deciphering the mechanisms underlying mammalian regeneration. Nelson et al. show that dsRNA released from damaged skin triggers TLR3 activation and the downstream effector pathways IL-6/Stat3, leading to upregulation of hair follicle markers and activation of core hair morphogenetic programs.
  • Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia

    • Hyog Young Kwon,
    • Jeevisha Bajaj,
    • Takahiro Ito,
    • Allen Blevins,
    • Takaaki Konuma,
    • Joi Weeks,
    • Nikki K. Lytle,
    • Claire S. Koechlein,
    • David Rizzieri,
    • Charles Chuah,
    • Vivian G. Oehler,
    • Roman Sasik,
    • Gary Hardiman,
    • Tannishtha Reya
    Reya and colleagues identify Tetraspanin 3 as a key signal required for AML. Tspan3 deletion leads to improved survival in mouse models of AML and reduced cancer growth in xenografts. Tspan3 loss impairs migration of leukemic cells to SDF suggesting that it may influence oncogenesis by controlling a normal chemokine response.
  • Runx1 Deficiency Decreases Ribosome Biogenesis and Confers Stress Resistance to Hematopoietic Stem and Progenitor Cells

    • Xiongwei Cai,
    • Long Gao,
    • Li Teng,
    • Jingping Ge,
    • Zaw Min Oo,
    • Ashish R. Kumar,
    • D. Gary Gilliland,
    • Philip J. Mason,
    • Kai Tan,
    • Nancy A. Speck
    Loss-of-function RUNX1 mutations are common in myelodysplastic syndrome and leukemia and can be early events. Cai et al. demonstrate that Runx1 loss decreases ribosome biogenesis and translation in hematopoietic stem and progenitor cells and confers resistance to endogenous and genotoxic stress.
  • Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells

    • Kotaro Sasaki,
    • Shihori Yokobayashi,
    • Tomonori Nakamura,
    • Ikuhiro Okamoto,
    • Yukihiro Yabuta,
    • Kazuki Kurimoto,
    • Hiroshi Ohta,
    • Yoshinobu Moritoki,
    • Chizuru Iwatani,
    • Hideaki Tsuchiya,
    • Shinichiro Nakamura,
    • Kiyotoshi Sekiguchi,
    • Tetsushi Sakuma,
    • Takashi Yamamoto,
    • Takahide Mori,
    • Knut Woltjen,
    • Masato Nakagawa,
    • Takuya Yamamoto,
    • Kazutoshi Takahashi,
    • Shinya Yamanaka,
    • Mitinori Saitou
    Saitou and colleagues report induction of human primordial germ cell-like cells (hPGCLCs) from pluripotent stem cells. hPGCLC and mouse PGC specification rely on similar signaling pathways but utilize distinct transcriptional programs, highlighting differences in PGC induction and demonstrating the utility of hPGCLCs for studying human germ cell development in vitro.

Short Articles

Resources

  • CRISPR-Cas9-Mediated Genetic Screening in Mice with Haploid Embryonic Stem Cells Carrying a Guide RNA Library

    • Cuiqing Zhong,
    • Qi Yin,
    • Zhenfei Xie,
    • Meizhu Bai,
    • Rui Dong,
    • Wei Tang,
    • Yu-Hang Xing,
    • Hongling Zhang,
    • Suming Yang,
    • Ling-Ling Chen,
    • Marisa S. Bartolomei,
    • Anne Ferguson-Smith,
    • Dangsheng Li,
    • Li Yang,
    • Yuxuan Wu,
    • Jinsong Li
    Li and colleagues show that the combined application of altered expression of two imprinted genes and CRISPR-Cas9-based genome editing allows the efficient and stable generation of gene-modified semi-cloned mice from androgenetic haploid embryonic stem cells. This approach has potential for mutagenesis and screening.
  • Engineering Human Stem Cell Lines with Inducible Gene Knockout using CRISPR/Cas9

    • Yuejun Chen,
    • Jingyuan Cao,
    • Man Xiong,
    • Andrew J. Petersen,
    • Yi Dong,
    • Yunlong Tao,
    • Cindy Tzu-Ling Huang,
    • Zhongwei Du,
    • Su-Chun Zhang
    By combining CRISPR/Cas9-mediated genome editing with the Flp/FRT and Cre/LoxP system, Chen et al. developed an efficient two-step strategy to generate inducible gene knockout hPSC lines with predictable gene mutations upon tamoxifen treatment at any stages of differentiation. The iKO hPSC lines will enable the elucidation of gene functions throughout differentiation.

Errata

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