Abstract：
:Pelizaeus-Merzbacher disease (PMD) is a fatal X-linked disorder caused by loss of myelinating oligodendrocytes and consequent hypomyelination. The underlying cellular and molecular dysfunctions are not fully defined, but therapeutic enhancement of oligodendrocyte survival could restore functional myelination in patients. Here we generated pure, scalable quantities of induced pluripotent stem cell-derived oligodendrocyte progenitor cells (OPCs) from a severe mouse model of PMD, Plp1jimpy. Temporal phenotypic and transcriptomic studies defined an early pathological window characterized by endoplasmic reticulum (ER) stress and cell death as OPCs exit their progenitor state. High-throughput phenotypic screening identified a compound, Ro 25-6981, which modulates the ER stress response and rescues mutant oligodendrocyte survival in jimpy, in vitro and in vivo, and in human PMD oligocortical spheroids. Surprisingly, increasing oligodendrocyte survival did not restore subsequent myelination, revealing a second pathological phase. Collectively, our work shows that PMD oligodendrocyte loss can be rescued pharmacologically and defines a need for multifactorial intervention to restore myelination.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Elitt MS,Shick HE,Madhavan M,Allan KC,Clayton BLL,Weng C,Miller TE,Factor DC,Barbar L,Nawash BS,Nevin ZS,Lager AM,Li Y,Jin F,Adams DJ,Tesar PJdoi
10.1016/j.stemcr.2018.07.015subject
Has Abstractpub_date
2018-09-11 00:00:00pages
711-726issue
3issn
2213-6711pii
S2213-6711(18)30320-5journal_volume
11pub_type
杂志文章abstract：:The environment surrounding stem cells has the ability to elicit profound, heritable epigenetic changes orchestrated by multiple epigenetic mechanisms, which can be modulated by the level of specific metabolites. In this review, we highlight the significance of metabolism in regulating stem cell homeostasis, cell stat...
journal_title：Stem cell reports
pub_type： 杂志文章,评审
doi：10.1016/j.stemcr.2019.09.003
更新日期：2019-10-08 00:00:00
abstract：:The chromatin of naive embryonic stem cells (ESCs) has a largely open configuration, as evident by the lack of condensed heterochromatin and the hypomethylation of DNA. Several molecular mechanisms promoting this constellation were previously identified. Here we present evidence for an important epigenetic function of...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.02.011
更新日期：2017-04-11 00:00:00
abstract：:Being able to summarize properly your work is not an easy task. But learning the skill of writing a good abstract is very important, as it can open many doors, including the possibility to be selected as a speaker at conferences. As meeting abstract reviewers, here we are writing to give you insights into the abstract...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.11.016
更新日期：2018-12-11 00:00:00
abstract：:The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs) into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how N...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.03.005
更新日期：2014-04-18 00:00:00
abstract：:Ischemic stroke enhances the proliferation of adult-generated precursor cells that ectopically migrate toward the infarct. Studies have correlated precursor cell proliferation and subsequent adult neurogenesis with enhanced stroke recovery, yet it remains unclear whether stroke can generate new neurons capable of func...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.10.011
更新日期：2018-12-11 00:00:00
abstract：:Activation of Wnt/β-catenin signaling can induce both self-renewal and differentiation in naive pluripotent embryonic stem cells (ESCs). To gain insights into the mechanism by which Wnt/β-catenin regulates ESC fate, we screened and characterized its downstream targets. Here, we show that the self-renewal-promoting eff...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.07.014
更新日期：2015-09-08 00:00:00
abstract：:The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiP...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.10.019
更新日期：2018-12-11 00:00:00
abstract：:Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.05.001
更新日期：2014-06-03 00:00:00
abstract：:Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with g...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.10.001
更新日期：2013-11-07 00:00:00
abstract：:Cell transplantation into immunodeficient recipients is a widely used approach to study stem cell and cancer biology; however, studying cell states post transplantation in vivo is inconvenient in mammals. Here, we generated a foxn1/Casper mutant zebrafish that is transparent and exhibits T cell deficiency. By employin...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.07.020
更新日期：2020-09-08 00:00:00
abstract：:The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed compr...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.05.006
更新日期：2016-07-12 00:00:00
abstract：:Human pluripotent stem cells are a valuable resource for transplantation, yet our ability to profile xenografts is largely limited to low-throughput immunohistochemical analysis by difficulties in readily isolating grafts for transcriptomic and/or proteomic profiling. Here, we present a simple methodology utilizing di...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.10.001
更新日期：2019-11-12 00:00:00
abstract：:Insertion of reporter cassettes into the Lgr5 locus has enabled the characterization of mouse intestinal stem cells (ISCs). However, low cell surface abundance of LGR5 protein and lack of high-affinity anti-LGR5 antibodies represent a roadblock to efficiently isolate human colonic stem cells (hCoSCs). We set out to id...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.10.003
更新日期：2015-12-08 00:00:00
abstract：:Pig embryonic stem cells (pESCs) have been considered an important candidate for preclinical research on human therapies. However, the lack of understanding of pig pluripotent networks has hampered establishment of authentic pESCs. Here, we report that FGF2, ACTVIN, and WNT signaling are essential to sustain pig pluri...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.05.028
更新日期：2019-07-09 00:00:00
abstract：:Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.12.012
更新日期：2018-02-13 00:00:00
abstract：:Long-term survival and integration of neural progenitor cells (NPCs) transplanted following spinal cord injury (SCI) have been observed. However, questions concerning the differentiation choice, the mechanism of action, and the contribution of NPCs to functional recovery remains unanswered. Therefore, we investigated ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.03.013
更新日期：2019-05-14 00:00:00
abstract：:The differentiation of pluripotent stem cells to hepatocytes is well established, yet current methods suffer from several drawbacks. These include a lack of definition and reproducibility, which in part stems from continued reliance on recombinant growth factors. This has remained a stumbling block for the translation...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.04.001
更新日期：2015-05-12 00:00:00
abstract：:Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the poss...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.02.015
更新日期：2017-04-11 00:00:00
abstract：:Spermatogonial stem cells (SSCs) serve as a resource for producing genetically modified animals. However, genetic manipulation of SSCs has met with limited success. Here, we show efficient gene transfer into SSCs via a lentivirus (FV-LV) using a fusion protein (F), a Sendai virus (SV) envelope protein involved in viri...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.02.001
更新日期：2020-03-10 00:00:00
abstract：:Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) could potentially provide unlimited HSCs for clinical transplantation, a curative treatment for numerous blood diseases. However, to date, bona fide HSC generation has been largely unsuccessful in vitro. We have previously described proof...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.08.010
更新日期：2017-10-10 00:00:00
abstract：:Direct cardiac reprogramming holds great potential for regenerative medicine. However, it remains inefficient, and induced cardiomyocytes (iCMs) generated in vitro are less mature than those in vivo, suggesting that undefined extrinsic factors may regulate cardiac reprogramming. Previous in vitro studies mainly used h...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.07.022
更新日期：2020-09-08 00:00:00
abstract：:The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicat...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.05.010
更新日期：2014-06-19 00:00:00
abstract：:Human pluripotent stem cells (hPSCs) offer a renewable source of cells that can be expanded indefinitely and differentiated into virtually any type of cell in the human body, including neurons. This opens up unprecedented possibilities to study neuronal cell and developmental biology and cellular pathology of the nerv...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.05.010
更新日期：2016-06-14 00:00:00
abstract：:Hematopoietic stem cells (HSCs) ensure a life-long regeneration of the blood system and are therefore an important source for transplantation and gene therapy. The teratoma environment supports the complex development of functional HSCs from human pluripotent stem cells, which is difficult to recapitulate in culture. ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.09.010
更新日期：2018-11-13 00:00:00
abstract：:Thyroid hormone (TH) transporters are required for the transmembrane passage of TH in target cells. In humans, inactivating mutations in the TH transporter MCT8 cause the Allan-Herndon-Dudley syndrome, characterized by severe neuromuscular symptoms and an abnormal TH serum profile, which is fully replicated in Mct8 kn...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.03.021
更新日期：2018-06-05 00:00:00
abstract：:Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.01.002
更新日期：2018-02-13 00:00:00
abstract：:In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous Kit(Wv) mutations into C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS) strongly promoted human multi-lineage reconstitution. After xenotransplantation of h...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.07.002
更新日期：2016-09-13 00:00:00
abstract：:In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs) leads to re...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.12.012
更新日期：2015-02-10 00:00:00
abstract：:Heterozygous de novo mutations in GATA6 are the most frequent cause of pancreatic agenesis in humans. In mice, however, a similar phenotype requires the biallelic loss of Gata6 and its paralog Gata4. To elaborate the human-specific requirements for GATA6, we chose to model GATA6 loss in vitro by combining both gene-ed...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.12.003
更新日期：2019-01-08 00:00:00
abstract：:Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) entails a mesenchymal to epithelial transition (MET). While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD) of the epithelial-to-mesenchymal transition (EMT) factor SNAI1 (SNAIL) paradoxically reduce...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.09.008
更新日期：2014-11-11 00:00:00
