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Jul 13, 2021

Volume 16Issue 7p1645-1846
Open Access
Cover In their study, Liu et al. (1805–1817) show that retinal organoid-derived C-Kit+/SSEA-1 (C-Kit+) retinal progenitor cells (RPCs) successfully integrate into three major layers of advanced degenerative retina, form functional synapses with the hosts, and connect with the neural circuits. With the help of a genetically encoded calcium indicator (GECI), they visually demonstrate synaptic repair and vision restoration. The cover image illustrates the migration of the engrafted C-Kit+ RPCs on a flat mount of recipient retina. The RPCs have been labeled with GECI (GCaMP5, green). The cover image “rebirth,” which is a combination of a retinal mount photograph with a butterfly silhouette, symbolizes stem cell transplantation regenerating the retina, in allusion to a caterpillar's metamorphosis into a fascinating butterfly. Image courtesy of the authors....
Cover In their study, Liu et al. (1805–1817) show that retinal organoid-derived C-Kit+/SSEA-1 (C-Kit+) retinal progenitor cells (RPCs) successfully integrate into three major layers of advanced degenerative retina, form functional synapses with the hosts, and connect with the neural circuits. With the help of a genetically encoded calcium indicator (GECI), they visually demonstrate synaptic repair and vision restoration. The cover image illustrates the migration of the engrafted C-Kit+ RPCs on a flat mount of recipient retina. The RPCs have been labeled with GECI (GCaMP5, green). The cover image “rebirth,” which is a combination of a retinal mount photograph with a butterfly silhouette, symbolizes stem cell transplantation regenerating the retina, in allusion to a caterpillar's metamorphosis into a fascinating butterfly. Image courtesy of the authors.

Editorial

  • Updates for contributors: Rigor and reproducibility in stem cell research

    • Martin Pera
    The initial assessment of any manuscript submitted to Stem Cell Reports is carried out by the Editor-in-Chief, in collaboration with our Managing Editor, Dr. Yvonne Fischer, often in consultation with our associate editors and our editorial board. For original research studies, we undertake a general evaluation of the novelty of the study, its overall interest to our readership, and the quality of the experimental design and data. Unfortunately, we find all too frequently that we are forced to return manuscripts to authors prior to review in order to clarify significant concerns about rigor and reproducibility: questions about the design of experiments (for example, the nature and number of experimental replicates), statistical analyses, statistical inference, data presentation and visualization, and the use of sufficient numbers of stem cell lines and subclones in disease modeling studies and resource studies reporting new experimental techniques.

Letters

  • Questioning the evidence for a Janus-faced nature of adult neurogenesis in Alzheimer’s disease

    • Trongha Phan,
    • Muskan Gupta,
    • Rachana Mishra,
    • Pavan Kumar,
    • Ahmed Disouky,
    • Terilyn K.L. Stephen,
    • Karen Rakowiecki,
    • Orly Lazarov
    A substantial number of studies support the notion that hippocampal neurogenesis is deficient in mouse models of Familial Alzheimer’s disease (FAD) as well as in Alzheimer’s disease (AD) patients (Disouky and Lazarov, 2021). In agreement with that, interventions that upregulate neurogenesis have led to the attenuation of pathology and rescue of memory impairments (see for example Choi et al., 2018). Likewise, previous studies have showed that ablating neurogenesis in FAD mice exacerbated learning and memory (Choi et al., 2018; Hollands et al., 2017).
  • Response to questioning the evidence for a Janus-faced nature of adult neurogenesis in Alzheimer's disease

    • Xiaoqing Zhang,
    • Yufei Mei,
    • Jing Wang,
    • Xiaojie Wei,
    • Binggui Sun
    Adult hippocampal neurogenesis (AHN) is impaired in mouse models of Alzheimer’s disease (AD) and AD patients (Krezymon et al., 2013; Moreno-Jiménez et al., 2019; Sun et al., 2009; Toda et al., 2019). An obvious assumption, therefore, is that enhancing AHN will ameliorate, while inhibiting AHN will exacerbate, the pathology and memory deficits in AD. Recently, we examined the effects of inhibiting AHN on synaptic and cognitive functions in AD mice by using two AD models with two approaches to inhibit AHN.

Forum

Perspective

  • Recognizing the ethical implications of stem cell research: A call for broadening the scope

    • Lars S. Assen,
    • Karin R. Jongsma,
    • Rosario Isasi,
    • Marianna A. Tryfonidou,
    • Annelien L. Bredenoord
    The ethical implications of stem cell research are often discussed in terms of risks, side effects, and safety, which are examples of hard impacts. In this article, Assen and colleagues argue that to understand the broader spectrum of ethical implications of stem cell research on science and society, it is important to recognize the so-called soft impacts.

Review

  • Mesenchymal stromal cell-derived exosomes in cardiac regeneration and repair

    • Si-Jia Sun,
    • Rui Wei,
    • Fei Li,
    • Song-Yan Liao,
    • Hung-Fat Tse
    In this article Liao, Tse and colleagues summarize the mechanisms that underlie the therapeutic efficacy of MSC-derived exosomes in cardiac regeneration and repair and their potential role in enhancing the therapeutic efficacy of cell-based therapy. Moreover, they discuss the potential approaches to improve the production and therapeutic effects of MSC-derived exosomes.

Meeting report

  • From development toward therapeutics, a collaborative effort on blood progenitors

    • Avik Choudhuri,
    • Tianxiao Han,
    • Leonard I. Zon
    The National Heart, Lung, and Blood Institute Progenitor Cell Translational Consortium Blood Progenitor Meeting was hosted virtually on November 5, 2020, with 93 attendees across 20 research groups. The purpose of this meeting was to exchange recent findings, discuss current efforts, and identify prospective opportunities in the field of hematopoietic stem and progenitor cell research and therapeutic discovery.

Reports

  • Derivation of feeder-free human extended pluripotent stem cells

    • Ran Zheng,
    • Ting Geng,
    • Dan-Ya Wu,
    • Tianzhe Zhang,
    • Hai-Nan He,
    • Hai-Ning Du,
    • Donghui Zhang,
    • Yi-Liang Miao,
    • Wei Jiang
    In this article, Zheng et al. establish human feeder-free extended pluripotent stem cells (ffEPSCs) from ESCs and iPSCs and characterize the extended pluripotency in terms of molecular markers and bidirectional developmental ability. They further identify that chemicals targeting histone modifiers andglycolysis could facilitate the transition and maintenance of ffEPSCs.
  • Human pluripotent stem cell-derived eosinophils reveal potent cytotoxicity against solid tumors

    • Weifeng Lai,
    • Huangfan Xie,
    • Yuting Liu,
    • Feng Zheng,
    • Yingfeng Zhang,
    • Qi Lei,
    • Lejun Lv,
    • Jiebin Dong,
    • Jian Song,
    • Xue Gao,
    • Ming Yin,
    • Chengyan Wang,
    • Hongkui Deng
    In this article, Deng and colleagues establish an efficient chemically defined protocol to generate functional eosinophils from hPSCs, which show competent tumor killing capacity in vitro and in vivo. In addition, the combination of hPSC-derived eosinophils with CAR-T cells exhibits potential synergistic effects suppressing tumor growth. This study opens up a new avenue for developing eosinophil-based immunotherapies against solid tumors.

Articles

  • Uncoupling key determinants of hematopoietic stem cell engraftment through cell-specific and temporally controlled recipient conditioning

    • Natsumi Miharada,
    • Anna Rydström,
    • Justyna Rak,
    • Jonas Larsson
    In this study Larsson and colleagues show that selective and temporally controlled depletion of resident hematopoietic stem cells (HSCs) through genetic deletion of Gata2 constitutes efficient recipient conditioning for transplantation without irradiation. They demonstrate that engraftment in a non-perturbed microenvironment uniquely challenges properties affecting homing and early HSC localization, that otherwise are masked in irradiated recipients.
  • Sequential regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium by Ezh1/2

    • Rebecca A. Soto,
    • Mohamad Ali T. Najia,
    • Mariam Hachimi,
    • Jenna M. Frame,
    • Gabriel A. Yette,
    • Edroaldo Lummertz da Rocha,
    • Kryn Stankunas,
    • George Q. Daley,
    • Trista E. North
    Here, North and colleagues reveal Ezh1 as a key regulator of the developmental shift from arterial fate toward hemogenic potential and subsequent HSPC formation in the embryonic dorsal aorta. Significantly, the related PRC2 subunit, Ezh2, which is upregulated in response to Ezh1 loss, has no impact on arterial state, but is required downstream of Ezh1 to regulate HSPC production.
  • Differentiation of human induced pluripotent stem cells to authentic macrophages using a defined, serum-free, open-source medium

    • Alun Vaughan-Jackson,
    • Szymon Stodolak,
    • Kourosh H. Ebrahimi,
    • Cathy Browne,
    • Paul K. Reardon,
    • Elisabete Pires,
    • Javier Gilbert-Jaramillo,
    • Sally A. Cowley,
    • William S. James
    Vaughan-Jackson et al. sought to bring transparency and malleability to the composition of growth media for human iPSC-derived macrophages. They describe a new, simple, defined, and open-sourced medium which supports the growth of macrophages. Building upon previous methodologies for iPSC-derived macrophage differentiation, they improve terminal differentiation and provide fully competent authentic tissue-derived macrophages.
  • Lesch-Nyhan disease causes impaired energy metabolism and reduced developmental potential in midbrain dopaminergic cells

    • Scott Bell,
    • Vincent McCarty,
    • Huashan Peng,
    • Malvin Jefri,
    • Nuwan Hettige,
    • Lilit Antonyan,
    • Liam Crapper,
    • Liam A. O'Leary,
    • Xin Zhang,
    • Ying Zhang,
    • Hanrong Wu,
    • Diane Sutcliffe,
    • Ilaria Kolobova,
    • Thad A. Rosenberger,
    • Luc Moquin,
    • Alain Gratton,
    • Jelena Popic,
    • Ilse Gantois,
    • Patrick S. Stumpf,
    • Andreas A. Schuppert,
    • Naguib Mechawar,
    • Nahum Sonenberg,
    • Michel L. Tremblay,
    • Hyder A. Jinnah,
    • Carl Ernst
    Ernst and colleagues show neuronal cell-type-specific effects of cell-fate markers and oxidative phosphorylation capacity from HPRT-deficient cells, providing mechanistic insight into the neurological features of Lesch-Nyhan disease.
  • Efficient generation of dopaminergic induced neuronal cells with midbrain characteristics

    • Yi Han Ng,
    • Soham Chanda,
    • Justyna A. Janas,
    • Nan Yang,
    • Yuko Kokubu,
    • Thomas C. Südhof,
    • Marius Wernig
    Dopaminergic neurons can be induced from pluripotent cells using overexpression of transcription factors. Existing transcription factor combinations result in cells of mixed regional identity. Here, Wernig and colleagues report that with extracellular signals, a six-factor combination delivered via piggyBac transposons is capable of inducing dopamine neurons of central identity from mouse and human embryonic stem cells.
  • Reprogramming astrocytes to motor neurons by activation of endogenous Ngn2 and Isl1

    • Meiling Zhou,
    • Xiaoqing Tao,
    • Ming Sui,
    • Mengge Cui,
    • Dan Liu,
    • Beibei Wang,
    • Ting Wang,
    • Yunjie Zheng,
    • Juan Luo,
    • Yangling Mu,
    • Feng Wan,
    • Ling-Qiang Zhu,
    • Bin Zhang
    In the current study, Bin Zhang and colleagues use a CRISPRa system to activate two transcriptional factors in astrocytes and convert these cells into motor neurons in vitro and in vivo. The converted neurons can function as endogenous motor neurons, thus providing a novel approach to the repair of injured spinal cord and establishment of a motor neuron-related disease model.
  • Endogenous neural stem cells modulate microglia and protect against demyelination

    • Béatrice Brousse,
    • Océane Mercier,
    • Karine Magalon,
    • Fabrice Daian,
    • Pascale Durbec,
    • Myriam Cayre
    In this article, Cayre and colleagues show that following demyelination, corpus callosum areas enriched in subventricular zone-derived progenitors (SVZdNPs) are less affected, and microglial cells exhibit an immunomodulatory phenotype. Mobilized SVZdNPs produce MFGE8 promoting myelin debris phagocytosis in vitro. Their results highlight immunomodulatory properties of endogenous progenitors for myelin regeneration.
  • Synaptic repair and vision restoration in advanced degenerating eyes by transplantation of retinal progenitor cells

    • Xiang-Yu He,
    • Cong-Jian Zhao,
    • Haiwei Xu,
    • Kang Chen,
    • Bai-Shi-Jiao Bian,
    • Yu Gong,
    • Chuan-Huang Weng,
    • Yu-Xiao Zeng,
    • Yan Fu,
    • Yong Liu,
    • Zheng-Qin Yin
    In this article Liu, Yin, and colleagues show C-Kit+ retinal progenitor cells can migrate and integrate in three major layers of advanced degenerative retina, form functional synapses with the hosts, and connect with the neural circuits. They provide state-of-the-art techniques to visually demonstrate exceptional synaptic repair and vision restoration, opening up a feasible avenue for advanced RD treatment.
  • Auxin-degron system identifies immediate mechanisms of OCT4

    • Lawrence E. Bates,
    • Mariana R.P. Alves,
    • José C.R. Silva
    In this article, Silva and colleagues show that the initial response to the loss of OCT4 in mouse nPSCs is epigenetic and transcriptional silencing of key pluripotency genes, followed by the expression of trophectoderm-associated genes. Furthermore, they demonstrate that NANOG maintains its capacity to bind to the genome, and this is enhanced in the absence of OCT4.
  • Spermatogonial stem cell transplantation into nonablated mouse recipient testes

    • Hiroko Morimoto,
    • Narumi Ogonuki,
    • Mito Kanatsu-Shinohara,
    • Shogo Matoba,
    • Atsuo Ogura,
    • Takashi Shinohara
    In this article, Shinohara and colleagues show that spermatogonial stem cells can colonize and produce offspring in nonablated recipients.

Correction

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