Abstract：
:The bile salt export pump (BSEP) is responsible for the export of bile acid from hepatocytes. Impaired transcellular transport of bile acids in hepatocytes with mutations in BSEP causes cholestasis. Compensatory mechanisms to regulate the intracellular bile acid concentration in human hepatocytes with BSEP deficiency remain unclear. To define pathways that prevent cytotoxic accumulation of bile acid in hepatocytes, we developed a human induced pluripotent stem cell-based model of isogenic BSEP-deficient hepatocytes in a Transwell culture system. Induced hepatocytes (i-Heps) exhibited defects in the apical export of bile acids but maintained a low intracellular bile acid concentration by inducing basolateral export. Modeling the autoregulation of bile acids on hepatocytes, we found that BSEP-deficient i-Heps suppressed de novo bile acid synthesis using the FXR pathway via basolateral uptake and export without apical export. These observations inform the development of therapeutic targets to reduce the overall bile acid pool in patients with BSEP deficiency.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Hayashi H,Osaka S,Sakabe K,Fukami A,Kishimoto E,Aihara E,Sabu Y,Mizutani A,Kusuhara H,Naritaka N,Zhang W,Huppert SS,Sakabe M,Nakamura T,Hu YC,Mayhew C,Setchell K,Takebe T,Asai Adoi
10.1016/j.stemcr.2020.12.008subject
Has Abstractpub_date
2020-12-30 00:00:00issn
2213-6711pii
S2213-6711(20)30503-8pub_type
杂志文章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：: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：:Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.06.010
更新日期：2018-08-14 00:00:00
abstract：:We have developed an improved episomal vector system for efficient generation of integration-free induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells. More recently, we reported that the use of an optimized CRISPR-Cas9 system together with a double-cut donor increases homology-directed repai...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.04.013
更新日期：2018-06-05 00:00:00
abstract：:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate toward a ground state and may therefore...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.07.003
更新日期：2014-09-09 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：: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：: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 patien...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.07.015
更新日期：2018-09-11 00:00:00
abstract：:Human induced pluripotent stem cell (hiPSC) culture has become routine, yet the cost of pluripotent cell media, frequent medium changes, and the reproducibility of differentiation have remained restrictive. Here, we describe the formulation of a hiPSC culture medium (B8) as a result of the exhaustive optimization of m...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.12.007
更新日期：2020-02-11 00:00:00
abstract：:Differentiation of human embryonic stem cells into pancreatic β cells holds great promise for the treatment of diabetes. Recent advances have led to the production of glucose-responsive insulin-secreting cells in vitro, but resulting cells remain less mature than their adult primary β cell counterparts. The barrier(s)...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.11.009
更新日期：2020-01-14 00:00:00
abstract：:Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.10.015
更新日期：2017-12-12 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：:Induced pluripotent stem cells were created from a pancreas agenesis patient with a mutation in GATA6. Using genome-editing technology, additional stem cell lines with mutations in both GATA6 alleles were generated and demonstrated a severe block in definitive endoderm induction, which could be rescued by re-expressio...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.12.026
更新日期：2017-03-14 00:00:00
abstract：:Pro-fibrotic microenvironments of scars and tumors characterized by increased stiffness stimulate mesenchymal stromal cells (MSCs) to express α-smooth muscle actin (α-SMA). We investigated whether incorporation of α-SMA into contractile stress fibers regulates human MSC fate. Sorted α-SMA-positive MSCs exhibited high ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.05.004
更新日期：2015-06-09 00:00:00
abstract：:Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal loba...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.09.006
更新日期：2019-11-12 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：:Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP) processing and the accumulation of APP-derived amyloid β (Aβ) peptides are key proces...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.02.006
更新日期：2017-04-11 00:00:00
abstract：:Teratoma formation is the gold standard assay for testing the capacity of human pluripotent stem cells to differentiate into all embryonic germ layers. Although widely used, little effort has been made to transform this qualitative assay into a quantitative one. Using gene expression data from a wide variety of cells,...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.05.006
更新日期：2015-06-09 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：:Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.08.011
更新日期：2018-10-09 00:00:00
abstract：:Primordial germ cells (PGCs) are fate restricted to differentiate into gametes in vivo. However, when removed from their embryonic niche, PGCs undergo reversion to pluripotent embryonic germ cells (EGCs) in vitro. One of the major differences between EGCs and embryonic stem cells (ESCs) is variable methylation at impr...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.07.006
更新日期：2015-09-08 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：:Nerve-derived neural crest cells are essential for regeneration in certain animals, such as newts. Here, we asked whether they play a similar role during mammalian tissue repair, focusing on Sox2-positive neural crest precursors in skin. In adult skin, Sox2 was expressed in nerve-terminal-associated neural crest precu...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.04.004
更新日期：2013-06-04 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：: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：: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：: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：: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：: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：:Human mesenchymal stem cells (hMSCs), which conventionally are isolated based on their adherence to plastic, are heterogeneous and have poor growth and differentiation, limiting our ability to investigate their intrinsic characteristics. We report an improved prospective clonal isolation technique and reveal that the ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.06.001
更新日期：2013-07-11 00:00:00
