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

Sep 01, 2022

Volume 29Issue 9p1285-1420
On the cover: Two papers in this issue describe an emerging role for mitochondrial dynamics in regulating muscle stem cell function. Hong et al. (1298–1314) show that mitochondrial fission diminishes with age and stimulating fission boosts the proliferative capacity of muscle stem cells during regeneration and aging. In the context of muscle stem cell quiescence, Baker et al. (1315–1332) find that mitochondrial fragmentation controls stem cell activation and commitment. The cover image alludes to the dynamic structural plasticity of mitochondria in muscle stem cells described by these two studies. ©iStock.com/Love Employee....
On the cover: Two papers in this issue describe an emerging role for mitochondrial dynamics in regulating muscle stem cell function. Hong et al. (1298–1314) show that mitochondrial fission diminishes with age and stimulating fission boosts the proliferative capacity of muscle stem cells during regeneration and aging. In the context of muscle stem cell quiescence, Baker et al. (1315–1332) find that mitochondrial fragmentation controls stem cell activation and commitment. The cover image alludes to the dynamic structural plasticity of mitochondria in muscle stem cells described by these two studies. ©iStock.com/Love Employee.

Previews

  • Uncovering the origins and lineage markers of human heart fields

    • Matthew Miyamoto,
    • Chulan Kwon
    In this issue of Cell Stem Cell, Yang et al. devise a protocol for induction and differentiation of human heart-field precursors, drawing on inspiration from in vivo development. Intricate computational analyses uncovered conserved factors governing heart-field segregation, which facilitate enhanced study of human heart development and disease in the dish.
  • Fission impossible: Mitochondrial dynamics direct muscle stem cell fates

    • Ji-Hyung Lee,
    • Foteini Mourkioti
    Muscle stem cells (MuSCs) exhibit different metabolic profiles depending on their activity, however the mechanisms by which mitochondria affect MuSC fate has been understudied. In this issue of Cell Stem Cell, Hong et al. (2022) and Baker et al. (2022) demonstrate that defects in mitochondrial dynamics hinder proper MuSC activation and impair muscle regeneration.
  • Exploring the human extraembryonic mesoderm using naive pluripotent stem cells

    • Takumi Okubo,
    • Yasuhiro Takashima
    In this issue of Cell Stem Cell, Pham et al. report that naive human pluripotent stem cells can be differentiated into extraembryonic mesoderm cells (EXMCs). EXMCs are maintained for up to 70 days, resemble human and monkey extraembryonic mesoderm, and provide a model to study EXMC specification and function.
  • Lymphatic endothelia stakeout cryptic stem cells

    • Agne Antanaviciute,
    • Anjali Kusumbe,
    • Alison Simmons
    A trio of studies in this issue of Cell Stem Cell catalogs the anatomical and functional relationship of intestinal lymphatics with epithelial stem cells, defining an important niche role for the lymphatic endothelium.

Forum

  • Current status of cell-based interventions in Japan

    • Misao Fujita,
    • Taichi Hatta,
    • Kazuki Ide
    The Act on the Safety of Regenerative Medicine regulates cell-based interventions in Japan. Recent revisions to the law require disclosure of explanatory and consent materials for interventions seeking approval. In this Forum, we present an updated analysis of the status and challenges facing the Japanese regulatory framework.

Articles

  • Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy

    • Xiaotong Hong,
    • Joan Isern,
    • Silvia Campanario,
    • Eusebio Perdiguero,
    • Ignacio Ramírez-Pardo,
    • Jessica Segalés,
    • Pablo Hernansanz-Agustín,
    • Andrea Curtabbi,
    • Oleg Deryagin,
    • Angela Pollán,
    • José A. González-Reyes,
    • José M. Villalba,
    • Marco Sandri,
    • Antonio L. Serrano,
    • José A. Enríquez,
    • Pura Muñoz-Cánoves
    Open Access
    Hong et al. illustrate that mitochondrial dynamics are required for tissue regeneration. Mitochondrial fission facilitates stem cell function via OXPHOS and mitophagy regulation. The genetic (or aging-related) loss of the mitochondrial fission regulator DRP1 in muscle stem cells blunts their proliferation and regenerative capacity, whereas DRP1 re-establishment rescues these defects.
  • The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells

    • Nicole Baker,
    • Steven Wade,
    • Matthew Triolo,
    • John Girgis,
    • Damian Chwastek,
    • Sarah Larrigan,
    • Peter Feige,
    • Ryo Fujita,
    • Colin Crist,
    • Michael A. Rudnicki,
    • Yan Burelle,
    • Mireille Khacho
    Open Access
    Baker et al. identify a link between mitochondrial shape and the regulation of stem cell quiescence. Here, OPA1 and mitochondrial structural plasticity serve as a physiological rheostat that controls the depth of quiescence and activation potential of adult muscle stem cells. This hinges on the induction of a ROS/GSH-signaling mechanism.
  • Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

    • Gui-Wei He,
    • Lin Lin,
    • Jeff DeMartino,
    • Xuan Zheng,
    • Nadzeya Staliarova,
    • Talya Dayton,
    • Harry Begthel,
    • Willine J. van de Wetering,
    • Eduard Bodewes,
    • Jeroen van Zon,
    • Sander Tans,
    • Carmen Lopez-Iglesias,
    • Peter J. Peters,
    • Wei Wu,
    • Daniel Kotlarz,
    • Christoph Klein,
    • Thanasis Margaritis,
    • Frank Holstege,
    • Hans Clevers
    Open Access
    Generating a long-term organoid culture model that displays extensive budding and harbors all cell types of the human small intestine reveals mechanism of human Paneth cell differentiation by IL-22-mTOR signaling.
  • Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells

    • Thi Xuan Ai Pham,
    • Amitesh Panda,
    • Harunobu Kagawa,
    • San Kit To,
    • Cankat Ertekin,
    • Grigorios Georgolopoulos,
    • Sam S.F.A. van Knippenberg,
    • Ryan Nicolaas Allsop,
    • Alexandre Bruneau,
    • Jonathan Sai-Hong Chui,
    • Lotte Vanheer,
    • Adrian Janiszewski,
    • Joel Chappell,
    • Michael Oberhuemer,
    • Raissa Songwa Tchinda,
    • Irene Talon,
    • Sherif Khodeer,
    • Janet Rossant,
    • Frederic Lluis,
    • Laurent David,
    • Nicolas Rivron,
    • Bradley Philip Balaton,
    • Vincent Pasque
    Open Access
    Little is known about human embryos just after implantation. Pasque et al. established a human pluripotent stem cell-based model that recapitulates primate-specific differentiation into extraembryonic mesoderm cells, which represent a little-understood but major cell type thought to develop into several important lineages in the embryo.
  • Hepatic cytochrome P450 8B1 and cholic acid potentiate intestinal epithelial injury in colitis by suppressing intestinal stem cell renewal

    • Li Chen,
    • Tingying Jiao,
    • Weiwei Liu,
    • Yuhong Luo,
    • Jue Wang,
    • Xiaozhen Guo,
    • Xiao Tong,
    • Zemin Lin,
    • Chuying Sun,
    • Kanglong Wang,
    • Yifan He,
    • Yuwei Zhang,
    • Hualing Xu,
    • Jiawen Wang,
    • Jianping Zuo,
    • Qiurong Ding,
    • Shijun He,
    • Frank J. Gonzalez,
    • Cen Xie
    Xie and colleagues propose a regulatory mechanism of hepatic bile acid metabolism in colitis pathogenesis. They find that the hepatic CYP8B1-cholic acid metabolic axis impairs Lgr5+ intestinal stem cell renewal by repressing PPARα, thus exacerbating intestinal injury. Hepatic FXR activation or CYP8B1 knockout restores damaged epithelial barrier and alleviates colitis.

Resources

    Featured Article
  • Modeling human multi-lineage heart field development with pluripotent stem cells

    • Donghe Yang,
    • Juliana Gomez-Garcia,
    • Shunsuke Funakoshi,
    • Thinh Tran,
    • Ian Fernandes,
    • Gary D. Bader,
    • Michael A. Laflamme,
    • Gordon M. Keller
    We describe hPSC-derived models of FHF, aSHF, and pSHF development spanning the mesoderm, progenitor, and cardiomyocyte stages. Comparison between the hPSC-derived and the corresponding mouse populations revealed conserved developmental trajectories across the species. Access to cardiomyocyte subtypes derived from different heart fields enables modeling chamber-specific diseases and developing new therapies.
  • Single-cell analysis of embryoids reveals lineage diversification roadmaps of early human development

    • Yi Zheng,
    • Robin Zhexuan Yan,
    • Shiyu Sun,
    • Mutsumi Kobayashi,
    • Lifeng Xiang,
    • Ran Yang,
    • Alexander Goedel,
    • Yu Kang,
    • Xufeng Xue,
    • Sajedeh Nasr Esfahani,
    • Yue Liu,
    • Agnes M. Resto Irizarry,
    • Weisheng Wu,
    • Yunxiu Li,
    • Weizhi Ji,
    • Yuyu Niu,
    • Kenneth R. Chien,
    • Tianqing Li,
    • Toshihiro Shioda,
    • Jianping Fu
    Fu and colleagues profiled a stem cell-derived microfluidic amniotic sac embryoid (μPASE) using single-cell RNA sequencing. Molecular maps of lineage diversifications from the pluripotent human epiblast toward the amniotic ectoderm, primitive streak/mesoderm, and primordial germ cells were constructed and compared with in vivo primate data.
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