Abstract：
:Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed previous data generated in murine models and show that retromer stabilization has a potentially beneficial effect on amyloid beta generation from human stem cell-derived neurons. We further demonstrate that manipulation of retromer complex levels within neurons affects pathogenic TAU phosphorylation in an amyloid-independent manner. Taken together, our work demonstrates that retromer stabilization is a promising candidate for therapeutic development in AD and highlights the advantages of testing novel compounds in a human-specific, neuronal system.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Young JE,Fong LK,Frankowski H,Petsko GA,Small SA,Goldstein LSBdoi
10.1016/j.stemcr.2018.01.031subject
Has Abstractpub_date
2018-03-13 00:00:00pages
1046-1058issue
3issn
2213-6711pii
S2213-6711(18)30057-2journal_volume
10pub_type
杂志文章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：:Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-b...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.11.015
更新日期：2019-01-08 00:00:00
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：:Intestinal crypts have great capacity for repair and regeneration after intestinal stem cell (ISC) injury. Here, we define the cellular remodeling process resulting from ISC niche interruption by transient Notch pathway inhibition in adult mice. Although ISCs were retained, lineage tracing demonstrated a marked reduct...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.05.010
更新日期：2020-07-14 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：:We describe the use of a characteristic blue fluorescence to identify and isolate pluripotent human embryonic stem cells and human-induced pluripotent stem cells. The blue fluorescence emission (450-500 nm) is readily observed by fluorescence microscopy and correlates with the expression of pluripotency markers (OCT4,...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.05.004
更新日期：2014-06-12 00:00:00
abstract：:Robust production of terminally differentiated cells from self-renewing resident stem cells is essential to maintain proper tissue architecture and physiological functions, especially in high-turnover tissues. However, the transcriptional networks that precisely regulate cell transition and differentiation are poorly ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.01.003
更新日期：2020-02-11 00:00:00
abstract：:Following Jamie Thomson's lecture on primate embryonic stem cells (ESCs) at a meeting I had organized in March 1997, in Israel, to celebrate receipt of the Wolf Prize in Agriculture to my colleague and friend Neal First, frozen human embryos donated for research in Israel were shipped to Wisconsin. The five hESC lines...
journal_title：Stem cell reports
pub_type： 杂志文章,评审
doi：10.1016/j.stemcr.2018.04.011
更新日期：2018-05-08 00:00:00
abstract：:Human vision relies heavily upon cone photoreceptors, and their loss results in permanent visual impairment. Transplantation of healthy photoreceptors can restore visual function in models of inherited blindness, a process previously understood to arise by donor cell integration within the host retina. However, we and...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.12.008
更新日期：2018-02-13 00:00:00
abstract：:We identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an easy-to-use protocol for differentiating osteoclasts from human induced pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder, characterized by life-long progressive thickening of craniofacial bones and abnormal shape of long...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.09.016
更新日期：2017-11-14 00:00:00
abstract：:The in vitro derivation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is complicated by the existence of multiple overlapping embryonic blood cell programs called primitive, erythromyeloid progenitor (EMP), and definitive. As HSCs are only generated during the definitive stage of hematopoiesis,...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.07.008
更新日期：2015-08-11 00:00:00
abstract：:FAM122A is a highly conserved housekeeping gene, but its physiological and pathophysiological roles remain greatly elusive. Based on the fact that FAM122A is highly expressed in human CD71+ early erythroid cells, herein we report that FAM122A is downregulated during erythroid differentiation, while its overexpression ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.07.010
更新日期：2020-09-08 00:00:00
abstract：:Microglia have recently been established as key regulators of brain development. However, their role in neuronal subtype specification remains largely unknown. Using three different co-culture setups, we show that microglia-secreted factors enhance dopaminergic differentiation of somatic and induced pluripotent stem c...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.12.011
更新日期：2021-01-06 00:00:00
abstract：:Heterozygous mutations in the glucocerebrosidase gene (GBA) represent the strongest common genetic risk factor for Parkinson's disease (PD), the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independe...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.01.013
更新日期：2016-03-08 00:00:00
abstract：:Reappraisal of neuropathological studies suggests that pathological hallmarks of Alzheimer's disease and Parkinson's disease (PD) spread progressively along predictable neuronal pathways in the human brain through unknown mechanisms. Although there is much evidence supporting the prion-like propagation and amplificati...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.12.007
更新日期：2019-02-12 00:00:00
abstract：:In addition to their promise in regenerative medicine, pluripotent stem cells have proved to be faithful models of many human diseases. In particular, patient-specific stem cell-derived cardiomyocytes recapitulate key features of several life-threatening cardiac arrhythmia syndromes. For both modeling and regenerative...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.01.003
更新日期：2014-02-06 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：:The transition from naive to primed state of pluripotent stem cells is hallmarked by epithelial-mesenchymal transition, metabolic switch from oxidative phosphorylation to aerobic glycolysis, and changes in the epigenetic landscape. Since these changes are also seen as putative hallmarks of neoplastic cell transformati...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.01.004
更新日期：2018-03-13 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：:Organoids (ORGs) are increasingly used as models of cerebral cortical development. Here, we compared transcriptome and cellular phenotypes between telencephalic ORGs and monolayers (MONs) generated in parallel from three biologically distinct induced pluripotent stem cell (iPSC) lines. Multiple readouts revealed incre...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.12.019
更新日期：2021-01-20 00:00:00
abstract：:Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.11.008
更新日期：2013-12-12 00:00:00
abstract：:The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 comple...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.01.019
更新日期：2018-03-13 00:00:00
abstract：:Pluripotent cells emanate from the inner cell mass (ICM) of the blastocyst and when cultivated under optimal conditions immortalize as embryonic stem cells (ESCs). The fundamental mechanism underlying ESC derivation has, however, remained elusive. Recently, we have devised a highly efficient approach for establishing ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.08.006
更新日期：2017-10-10 00:00:00
abstract：:ADP-ribosylation factor-like 4aa (Arl4aa) is a member of the ADP-ribosylation factor family. It is expressed in hematopoietic tissue during embryonic development, but its function was unknown. Zebrafish arl4aa is preferentially expressed in the ventral wall of the dorsal aorta (VDA) at 24 and 36 hpf and in caudal hema...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.02.012
更新日期：2020-04-14 00:00:00
abstract：:Research in human induced pluripotent stem cells (hiPSCs) is rapidly developing and there are expectations that this research may obviate the need to use human embryonic stem cells (hESCs), the ethics of which has been a subject of controversy for more than 15 years. In this study, we investigated approximately 3,400 ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.03.002
更新日期：2015-05-12 00:00:00
abstract：:Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microgl...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.04.023
更新日期：2017-06-06 00:00:00
abstract：:Properties of cancer stem cells involved in drug resistance and relapse have significant effects on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myeloid leukemia (CML), TKIs have not fully cured CML due to TKI-resistant CML stem cells. Moreov...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.01.015
更新日期：2018-03-13 00:00:00
abstract：:The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). We have explored marrow ECM using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. We found that DPT cooperates with other ECM proteins to promote ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.07.021
更新日期：2017-09-12 00:00:00
abstract：:BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ)....
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.05.030
更新日期：2017-07-11 00:00:00
abstract：:Stem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepat...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.10.016
更新日期：2015-12-08 00:00:00
