当前位置： SCI文献检索 > Cell Stem Cell期刊下所有文献 > A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.

A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.

Abstract：

:Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Yan HHN,Siu HC,Law S,Ho SL,Yue SSK,Tsui WY,Chan D,Chan AS,Ma S,Lam KO,Bartfeld S,Man AHY,Lee BCH,Chan ASY,Wong JWH,Cheng PSW,Chan AKW,Zhang J,Shi J,Fan X,Kwong DLW,Mak TW,Yuen ST,Clevers H,Leung SY

doi

10.1016/j.stem.2018.09.016

subject

Has Abstract

pub_date

2018-12-06 00:00:00

pages

882-897.e11

issue

6

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(18)30480-6

journal_volume

23

pub_type

杂志文章

相关文献

Cell Stem Cell文献大全
  • Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons.

    abstract：:Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but it has ...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2016.05.002

    authors： Oh Y,Cho GS,Li Z,Hong I,Zhu R,Kim MJ,Kim YJ,Tampakakis E,Tung L,Huganir R,Dong X,Kwon C,Lee G

    更新日期：2016-07-07 00:00:00

  • Distinguishing mast cell and granulocyte differentiation at the single-cell level.

    abstract：:The lineage restriction of prospectively isolated hematopoietic progenitors has been traditionally assessed by bulk in vitro culture and transplantation of large number of cells in vivo. These methods, however, cannot distinguish between homogenous multipotent or heterogeneous lineage-restricted populations. Using clo...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2010.02.013

    authors： Franco CB,Chen CC,Drukker M,Weissman IL,Galli SJ

    更新日期：2010-04-02 00:00:00

  • Wnt-related molecules and signaling pathway equilibrium in hematopoiesis.

    abstract：:There is near consensus that Wnt family molecules establish important gradients within niches where hematopoietic stem cells (HSC) reside. We review recent papers suggesting that a delicate balance is required between competing Wnt ligands and corresponding signaling pathways to maintain HSC integrity. Some steps in t...

    journal_title：Cell stem cell

    pub_type： 杂志文章,评审

    doi：10.1016/j.stem.2008.12.004

    authors： Malhotra S,Kincade PW

    更新日期：2009-01-09 00:00:00

  • mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging.

    abstract：:Epidermal integrity is a complex process established during embryogenesis and maintained throughout the organism lifespan by epithelial stem cells. Although Wnt regulates normal epithelial stem cell renewal, aberrant Wnt signaling can contribute to cancerous growth. Here, we explored the consequences of persistent exp...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2009.06.017

    authors： Castilho RM,Squarize CH,Chodosh LA,Williams BO,Gutkind JS

    更新日期：2009-09-04 00:00:00

  • The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?

    abstract：:Cancer stem cells (CSCs) are tumor cells that have the principal properties of self-renewal, clonal tumor initiation capacity, and clonal long-term repopulation potential. CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment. These niches maintain the principle properties of...

    journal_title：Cell stem cell

    pub_type： 杂志文章,评审

    doi：10.1016/j.stem.2015.02.015

    authors： Plaks V,Kong N,Werb Z

    更新日期：2015-03-05 00:00:00

  • Sowing the Seeds of Clonal Hematopoiesis.

    abstract：:As humans age, hematopoietic stem cells (HSCs) occasionally acquire mutations in genes including DNMT3A that enable them to outcompete other HSCs and increase leukemia risk. In this issue of Cell Stem Cell, Tovy et al. (2020) report a previously uncharacterized mechanism by which DNMT3A loss confers increased fitness ...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2020.07.011

    authors： Liggett LA,Voit RA,Sankaran VG

    更新日期：2020-08-06 00:00:00

  • A Transient Developmental Hematopoietic Stem Cell Gives Rise to Innate-like B and T Cells.

    abstract：:The generation of distinct hematopoietic cell types, including tissue-resident immune cells, distinguishes fetal from adult hematopoiesis. However, the mechanisms underlying differential cell production to generate a layered immune system during hematopoietic development are unclear. Using an irreversible lineage-trac...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2016.08.013

    authors： Beaudin AE,Boyer SW,Perez-Cunningham J,Hernandez GE,Derderian SC,Jujjavarapu C,Aaserude E,MacKenzie T,Forsberg EC

    更新日期：2016-12-01 00:00:00

  • Tales from the Cryptkeeper: New Roles for Lats1/2 in Wnt-driven Homeostasis.

    abstract：:In this issue of Cell Stem Cell, Li et al. (2020) reveal pivotal roles for Lats1/2 in adult, Wnt-mediated intestinal homeostasis through TEAD-dependent and -independent transcription. Loss of Lats1/2 mobilizes a previously unrecognized YAP/TAZ-Groucho/TLE interaction to suppress Wnt/TCF-mediated transcription, thereby...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2020.04.011

    authors： Fu V,Guan KL

    更新日期：2020-05-07 00:00:00

  • The human egg is back.

    abstract：:In a recent issue of Nature, Tachibana et al. (2009) conducted chromosomal transfer into recipient primate oocytes to yield live offspring or monkey ESCs with no contribution of donor mitochondria. The success of this technique may increase demand for human oocyte donation for research. ...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2009.09.009

    authors： Cibelli J

    更新日期：2009-10-02 00:00:00

  • Decoupling of tumor-initiating activity from stable immunophenotype in HoxA9-Meis1-driven AML.

    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

    authors： Gibbs KD Jr,Jager A,Crespo O,Goltsev Y,Trejo A,Richard CE,Nolan GP

    更新日期：2012-02-03 00:00:00

  • Autoimmune T cells lured to a FASL web of death by MSCs.

    abstract：:Achieving immune tolerance through cell transplantation is a promising approach for treating autoimmune disease. In this issue of Cell Stem Cell, Akiyama et al. (2012) demonstrate that human and mouse mesenchymal stem cells can induce immune suppression by attracting and killing autoreactive T cells, which stimulates ...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2012.04.013

    authors： Murphy WJ,Nolta JA

    更新日期：2012-05-04 00:00:00

  • Stem Cells Expand Insights into Human Brain Evolution.

    abstract：:Substantial expansion in the number of cerebral cortex neurons is thought to underlie cognitive differences between humans and other primates, although the mechanisms underlying this expansion are unclear. Otani et al. (2016) utilize PSC-derived brain organoids to study how species-specific differences in cortical pro...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2016.03.017

    authors： Dyer MA

    更新日期：2016-04-07 00:00:00

  • The nuclear lamina regulates germline stem cell niche organization via modulation of EGFR signaling.

    abstract：:Stem cell niche interactions have been studied extensively with regard to cell polarity and extracellular signaling. Less is known about the way in which signals and polarity cues integrate with intracellular structures to ensure appropriate niche organization and function. Here, we report that nuclear lamins function...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2013.05.003

    authors： Chen H,Chen X,Zheng Y

    更新日期：2013-07-03 00:00:00

  • Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation.

    abstract：:Adoptive immunotherapy with functional T cells is potentially an effective therapeutic strategy for combating many types of cancer and viral infection. However, exhaustion of antigen-specific T cells represents a major challenge to this type of approach. In an effort to overcome this problem, we reprogrammed clonally ...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2012.11.002

    authors： Nishimura T,Kaneko S,Kawana-Tachikawa A,Tajima Y,Goto H,Zhu D,Nakayama-Hosoya K,Iriguchi S,Uemura Y,Shimizu T,Takayama N,Yamada D,Nishimura K,Ohtaka M,Watanabe N,Takahashi S,Iwamoto A,Koseki H,Nakanishi M,Eto K,Na

    更新日期：2013-01-03 00:00:00

  • A Little Bit of Guidance: Mini Brains on Their Route to Adolescence.

    abstract：:Cerebral organoids represent a new model in which to study human brain development outside the human body. Recently in Nature Biotechnology, Lancaster et al. (2017) tackled the lack of reproducibility, tissue homogeneity, and complexity of this system by bioengineering organoids to establish the next generation of hum...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2017.07.001

    authors： Koch P,Ladewig J

    更新日期：2017-08-03 00:00:00

  • Out of Many, One: Computational Reconstruction of Mouse Skin using Single-Cell Transcriptomics.

    abstract：:Mammalian skin is a complex and heterogeneous tissue with several distinct compartments and stem cell populations. Joost et al. (2016) now use single-cell RNaseq to comprehensively reconstruct this complexity, revealing spatial and pseudotemporal differences between transcriptional programs in distinct compartments an...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2016.09.009

    authors： Chen JC,Christiano AM

    更新日期：2016-10-06 00:00:00

  • Pluripotency network in embryonic stem cells: maybe Leibniz was right all along.

    abstract：:The transcription factors Tcf3 and Nanog regulate many genes in embryonic stem cells, but according to two reports in this issue of Cell Stem Cell (Festuccia et al., 2012, Martello et al., 2012), only one, Esrrb, encoding an orphan nuclear hormone receptor, truly matters in the maintenance of self-renewal. ...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2012.09.005

    authors： Zwaka TP

    更新日期：2012-10-05 00:00:00

  • Won't You Be My Neighbor? Muscle Stem Cells Recruit Endothelial Cells to Their Niche.

    abstract：:The maintenance of a pool of quiescent satellite cells (muscle stem cells) is necessary for long-term muscle health. In this issue of Cell Stem Cell, Verma et al. (2018) show that satellite cells recruit endothelial cells to create a vascular niche and that cross-talk between endothelial and satellite cells is vital f...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2018.09.013

    authors： Collins BC,Kardon G

    更新日期：2018-10-04 00:00:00

  • Key endothelial signals required for hematopoietic recovery.

    abstract：:In this issue of Cell Stem Cell, Hooper et al. (2009) use a combination of immunohistochemistry and flow cytometry to characterize the bone marrow vasculature both before and after injury. The authors demonstrate that recovery of normal hematopoiesis after myelosuppressive insult is dependent upon endothelial VEGFR2. ...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2009.02.005

    authors： Porter RL,Calvi LM

    更新日期：2009-03-06 00:00:00

  • Mitochondrial Shapeshifting Impacts AML Stemness and Differentiation.

    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

    authors： Schimmer AD

    更新日期：2018-07-05 00:00:00

  • Metabolic regulation of hematopoietic stem cells in the hypoxic niche.

    abstract：:Tissue homeostasis over the life of an organism relies on both self-renewal and multipotent differentiation of stem cells. Hematopoietic stem cells (HSCs) reside in a hypoxic bone marrow environment, and their metabolic status is distinct from that of their differentiated progeny. HSCs generate energy mainly via anaer...

    journal_title：Cell stem cell

    pub_type： 杂志文章,评审

    doi：10.1016/j.stem.2011.09.010

    authors： Suda T,Takubo K,Semenza GL

    更新日期：2011-10-04 00:00:00

  • Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1.

    abstract：:Polycomb group (PcG) proteins are essential regulators of stem cells. PcG and trithorax group proteins mark developmental regulator gene promoters with bivalent domains consisting of overlapping repressive and activating histone modifications to keep them poised for activation in embryonic stem cells. Bmi1, a componen...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2010.01.005

    authors： Oguro H,Yuan J,Ichikawa H,Ikawa T,Yamazaki S,Kawamoto H,Nakauchi H,Iwama A

    更新日期：2010-03-05 00:00:00

  • Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming.

    abstract：:Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normalization methods, mu...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2019.05.020

    authors： Zhou Y,Liu Z,Welch JD,Gao X,Wang L,Garbutt T,Keepers B,Ma H,Prins JF,Shen W,Liu J,Qian L

    更新日期：2019-07-03 00:00:00

  • The adult Drosophila malpighian tubules are maintained by multipotent stem cells.

    abstract：:All animals must excrete the waste products of metabolism. Excretion is performed by the kidney in vertebrates and by the Malpighian tubules in Drosophila. The mammalian kidney has an inherent ability for recovery and regeneration after ischemic injury. Stem cells and progenitor cells have been proposed to be responsi...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2007.07.003

    authors： Singh SR,Liu W,Hou SX

    更新日期：2007-08-16 00:00:00

  • Context-Specific Transcription Factor Functions Regulate Epigenomic and Transcriptional Dynamics during Cardiac Reprogramming.

    abstract：:Ectopic expression of combinations of transcription factors (TFs) can drive direct lineage conversion, thereby reprogramming a somatic cell's identity. To determine the molecular mechanisms by which Gata4, Mef2c, and Tbx5 (GMT) induce conversion from a cardiac fibroblast toward an induced cardiomyocyte, we performed c...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2019.06.012

    authors： Stone NR,Gifford CA,Thomas R,Pratt KJB,Samse-Knapp K,Mohamed TMA,Radzinsky EM,Schricker A,Ye L,Yu P,van Bemmel JG,Ivey KN,Pollard KS,Srivastava D

    更新日期：2019-07-03 00:00:00

  • Cellular reprogramming in pursuit of immortality.

    abstract：:The discovery that phenotypic diversity among differentiated cells results from epigenetic and not genetic differences, and can be reset to restore pluripotency, promises revolutionary advances in medicine. I discuss how this and related seminal discoveries have brought us to an exciting future. ...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2012.11.014

    authors： Surani MA

    更新日期：2012-12-07 00:00:00

  • Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs.

    abstract：:Expansion of transposable elements (TEs) coincides with evolutionary shifts in gene expression. TEs frequently harbor binding sites for transcriptional regulators, thus enabling coordinated genome-wide activation of species- and context-specific gene expression programs, but such regulation must be balanced against th...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2019.03.012

    authors： Pontis J,Planet E,Offner S,Turelli P,Duc J,Coudray A,Theunissen TW,Jaenisch R,Trono D

    更新日期：2019-05-02 00:00:00

  • Self-Organizing 3D Human Trunk Neuromuscular Organoids.

    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-deriv...

    journal_title：Cell stem cell

    pub_type： 杂志文章

    doi：10.1016/j.stem.2019.12.007

    authors： 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 M

    更新日期：2020-02-06 00:00:00

  • An epigenomic road map for endoderm development.

    abstract：:While studies of organ development have traditionally relied on model organisms, recent advances in embryonic stem cell (ESC) culture allow investigation of organogenesis in human cells. Wang et al. (2015) employ this system to map the dynamic enhancer landscape during ESC differentiation to the endoderm derivatives p...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2015.03.006

    authors： Kaestner KH

    更新日期：2015-04-02 00:00:00

  • Translational control: a new dimension in embryonic stem cell network analysis.

    abstract：:Systems biology studies have revealed transcriptional networks and proteomic signatures critical for embryonic stem cell (ESC) function. In this issue of Cell Stem Cell, Sampath et al. (2008) demonstrate that translation is also differentially controlled in undifferentiated versus differentiated ESCs. ...

    journal_title：Cell stem cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.stem.2008.04.009

    authors： Chang WY,Stanford WL

    更新日期：2008-05-08 00:00:00