Abstract：
:Neuromuscular networks assemble during early human embryonic development and are essential for the control of body movement. Previous neuromuscular junction modeling efforts using human pluripotent stem cells (hPSCs) generated either spinal cord neurons or skeletal muscles in monolayer culture. Here, we use hPSC-derived axial stem cells, the building blocks of the posterior body, to simultaneously generate spinal cord neurons and skeletal muscle cells that self-organize to generate human neuromuscular organoids (NMOs) that can be maintained in 3D for several months. Single-cell RNA-sequencing of individual organoids revealed reproducibility across experiments and enabled the tracking of the neural and mesodermal differentiation trajectories as organoids developed and matured. NMOs contain functional neuromuscular junctions supported by terminal Schwann cells. They contract and develop central pattern generator-like neuronal circuits. Finally, we successfully use NMOs to recapitulate key aspects of myasthenia gravis pathology, thus highlighting the significant potential of NMOs for modeling neuromuscular diseases in the future.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Faustino Martins JM,Fischer C,Urzi A,Vidal R,Kunz S,Ruffault PL,Kabuss L,Hube I,Gazzerro E,Birchmeier C,Spuler S,Sauer S,Gouti Mdoi
10.1016/j.stem.2019.12.007subject
Has Abstractpub_date
2020-02-06 00:00:00pages
172-186.e6issue
2eissn
1934-5909issn
1875-9777pii
S1934-5909(19)30525-9journal_volume
26pub_type
杂志文章相关文献
Cell Stem Cell文献大全abstract：:Scientists are rarely immoral and seldom even amoral. The ethical principles that underlie much of their own work are shared with scientists in other countries to a much greater degree than the cultural and religious differences among those countries would lead one to expect. Like me, few will have had any formal trai...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2007.05.003
更新日期：2007-06-07 00:00:00
abstract：:Hematopoietic stem cells (HSCs) must at times exit quiescence to divide and produce differentiated blood cells. In this issue of Cell Stem Cell, Takubo et al. (2013) and Yu et al. (2013) show that these opposing actions require distinct metabolic programs to meet the changing energy demands of self-renewing HSCs. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2012.12.005
更新日期：2013-01-03 00:00:00
abstract：:Prognostic markers that capture leukemia stem cell (LSC) activity can be useful for the risk stratification of acute myeloid leukemia (AML) patients. In a recent issue of Nature, Ng et al. (2016) develop a prognostic score based on a 17-gene expression signature of LSCs to predict outcome in AML patients. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2017.02.010
更新日期：2017-03-02 00:00:00
abstract：:The metabolic state of quiescent hematopoietic stem cells (HSCs) is an important regulator of self-renewal, but it is unclear whether or how metabolic parameters contribute to HSC lineage specification and commitment. Here, we show that the commitment of human and murine HSCs to the erythroid lineage is dependent upon...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2014.06.002
更新日期：2014-08-07 00:00:00
abstract：:In this issue of Cell Stem Cell, Pei et al. (2018) demonstrate that leukemic stem cells (LSCs) have enhanced mitochondrial fission, which is positively regulated by FIS1. FIS1 is necessary to maintain LSC function; thus, targeting its expression and mitochondrial fission is a novel approach to decrease stemness and in...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2018.05.026
更新日期：2018-07-05 00:00:00
abstract：:Organoid techniques provide unique platforms to model brain development and neurological disorders. Whereas several methods for recapitulating corticogenesis have been described, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and re...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2017.07.007
更新日期：2017-09-07 00:00:00
abstract：:Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2011.03.010
更新日期：2011-05-06 00:00:00
abstract：:Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) can be achieved by viral-mediated transduction of defined transcription factors. Moving toward the eventual goal of clinical application, it is necessary to overcome limitations such as low reprogramming efficiency and genomic alterations due to ...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2009.03.005
更新日期：2009-04-03 00:00:00
abstract：:The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural p...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2016.11.014
更新日期：2016-12-01 00:00:00
abstract：:Stem-cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human pluripotent stem cells (hPSCs) differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2019.11.011
更新日期：2020-01-02 00:00:00
abstract：:The utility of induced pluripotent stem cells (iPSCs) as models to study diseases and as sources for cell therapy depends on the integrity of their genomes. Despite recent publications of DNA sequence variations in the iPSCs, the true scope of such changes for the entire genome is not clear. Here we report the whole-g...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.01.005
更新日期：2012-03-02 00:00:00
abstract：:Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2018.04.022
更新日期：2018-06-01 00:00:00
abstract：:Increasing evidence suggests tumors are maintained by cancer stem cells; however, their nature remains controversial. In a HoxA9-Meis1 (H9M) model of acute myeloid leukemia (AML), we found that tumor-initiating activity existed in three, immunophenotypically distinct compartments, corresponding to disparate lineages o...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.01.004
更新日期：2012-02-03 00:00:00
abstract：:To date, pluripotent epiblast stem cells (EpiSCs) had only been derived from postimplantation mouse embryos. In this issue of Cell Stem Cell, Najm et al. (2011) demonstrate that EpiSCs can be routinely derived from preimplantation embryos, showing that both human and mouse blastocysts can produce the same class of pri...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2011.02.009
更新日期：2011-03-04 00:00:00
abstract：:Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide th...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2019.08.004
更新日期：2019-10-03 00:00:00
abstract：:Stress can activate tumor-suppressive mechanisms, causing the loss of adult stem cell function with age. In this issue of Cell Stem Cell and in Nature, Castilho et al. (2009) and Harrison et al. (2009) highlight the importance of mTOR signaling in stem cell exhaustion and mammalian aging, respectively. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2009.08.008
更新日期：2009-09-04 00:00:00
abstract：:The identification of tumor-initiating cells represents a significant challenge for studies of prostate cancer. In a recent issue of Cell Reports, Agarwal and colleagues use organoid culture to ascertain two distinct luminal progenitors in a mouse model of prostate cancer, shedding new light on lineage relationships i...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2015.11.018
更新日期：2015-12-03 00:00:00
abstract：:We are only beginning to understand the higher-order chromatin structure of pluripotent stem cells and its relevance to cell fate. Three recent studies used different approaches to reconstruct the 3D chromatin landscape of naive and primed pluripotent cells, unveiling common features as well as differences between the...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2016.01.014
更新日期：2016-02-04 00:00:00
abstract：:The CRISPR-Cas9 system has been employed to generate mutant alleles in a range of different organisms. However, so far there have not been reports of use of this system for efficient correction of a genetic disease. Here we show that mice with a dominant mutation in Crygc gene that causes cataracts could be rescued by...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2013.10.016
更新日期：2013-12-05 00:00:00
abstract：:Knowledge of both the global chromatin structure and the gene expression programs of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) should provide a robust means to assess whether the genomes of these cells have similar pluripotent states. Recent studies have suggested that ESCs and iPSCs...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2010.06.015
更新日期：2010-08-06 00:00:00
abstract：:Leukemia stem cells (LSCs) are resistant to current therapies used to treat chronic myeloid leukemia (CML). Abraham et al. (2016) have identified a molecular network critical for CML LSC survival and propose that simultaneously targeting two of their major transcriptional regulators, p53 and c-Myc, may facilitate thei...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2016.06.005
更新日期：2016-07-07 00:00:00
abstract：:Understanding the development and maintenance of dopamine neurons is essential to establish novel stem cell therapies and animal models of Parkinson's disease. A recent PLoS Biology report (Kittappa et al., 2007) reveals that Foxa2 regulates dopamine neuron generation and differentiation, and that aging foxa2(+/-) mic...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2008.01.012
更新日期：2008-02-07 00:00:00
abstract：:Modifications of mRNAs can have a profound effect on cellular function and differentiation. In this issue of Cell Stem Cell, Batista et al. (2014) describe fundamental parameters of N(6)-methyl-adenosine modification of mRNAs in embryonic stem cells and provide strong evidence that modification plays a role in exit fr...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2014.11.011
更新日期：2014-12-04 00:00:00
abstract：:Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine dec...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2017.11.003
更新日期：2017-12-07 00:00:00
abstract：:Mouse embryonic stem cells (mESCs) cultured under serum/LIF conditions exhibit heterogeneous expression of pluripotency-associated factors that can be overcome by two inhibitors (2i) of the MEK and GSK3 pathways. Several studies have shown that the "ground state" induced by 2i is characterized by global hypomethylatio...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2015.07.005
更新日期：2015-10-01 00:00:00
abstract：:Patients with type 1 diabetes (T1D) often experience gastrointestinal enteropathy (DE) of unclear etiology. Now in Cell Stem Cell, D'Addio et al. (2015) utilize organoid culture models to study the roles of stem cells in DE and show that circulating IGF/IGFBP3 controls colonic stem cell function during homeostasis and...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2015.09.008
更新日期：2015-10-01 00:00:00
abstract：:COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and thei...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2020.06.011
更新日期：2020-07-02 00:00:00
abstract：:Exit from the naive pluripotent state occurs through a series of changes in the gene regulatory circuitry, allowing cells to become primed for lineage commitment. In this issue of Cell Stem Cell, Kalkan et al. (2019) show that three transcription regulators are required for naive mouse embryonic stem cells (ESCs) to e...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2019.04.008
更新日期：2019-05-02 00:00:00
abstract：:In response to muscle injury, satellite cells activate the p38α/β MAPK pathway to exit quiescence, then proliferate, repair skeletal muscle, and self-renew, replenishing the quiescent satellite cell pool. Although satellite cells are capable of asymmetric division, the mechanisms regulating satellite cell self-renewal...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.05.025
更新日期：2012-10-05 00:00:00
abstract：:N6-methyladenosine (m6A), the most abundant internal modification in mRNA, has been implicated in tumorigenesis. As an m6A demethylase, ALKBH5 has been shown to promote the development of breast cancer and brain tumors. However, in acute myeloid leukemia (AML), ALKBH5 was reported to be frequently deleted, implying a ...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2020.04.009
更新日期：2020-07-02 00:00:00
