Differentiated Troy⁺ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

Stange, Daniel E.,Koo, B.K.,Huch, M.,Sibbel, G.,Basak, O.,Lyubimova, A.,Kujala, P.,Bartfeld, S.,Koster, J.,Geahlen, Jessica H.,Peters, Peter J.,van Es, Johan H.,van de Wetering, M.,Mills, Jason C.,Cle Cell Press ; MIT Press 2013 Cell Vol.155 No.2

Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bidirectionally toward pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of fully differentiated chief cells. By lineage tracing with a Troy-eGFP-ires-CreERT2 allele, single marked chief cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy<SUP>+</SUP> chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific subset of chief cells that display plasticity in that they are capable of replenishing entire gastric units, essentially serving as quiescent ''reserve'' stem cells. These observations challenge the notion that stem cell hierarchies represent a ''one-way street.''

Gastrointestinal cancer organoids—applications in basic and translational cancer research

Seidlitz Therese,Stange Daniel E. 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Cancer is a major health problem and a leading cause of death worldwide. Early cancer detection and continuous changes in treatment strategies have improved overall patient survival. The recent development of targeted drugs offers new opportunities for personalized cancer treatment. Nevertheless, individualized treatment is accompanied by the need for biomarkers predicting the response of a patient to a certain drug. One of the most promising breakthroughs in recent years that might help to overcome this problem is the organoid technology. Organoid cultures exhibit self-renewal capacity, self-organization, and long-term proliferation, while recapitulating many aspects of their primary tissue. Generated patient-derived organoid (PDO) libraries constitute “living” biobanks, allowing the in-depth analysis of tissue function, development, tumor initiation, and cancer pathobiology. Organoids can be derived from all gastrointestinal tissues, including esophageal, gastric, liver, pancreatic, small intestinal and colorectal tissues, and cancers of these tissues. PDOs are amenable to various techniques, including sequencing analyses, drug screening, targeted therapy testing, tumor microenvironment studies, and genetic engineering capabilities. In this review, we discuss the different applications of gastrointestinal organoids in basic cancer biology and clinical translation.

細胞發育抑制劑 ENDOXAN-ASTA에 依한 婦人科癌의 治療

Lemke, J.,Stange, H-H,Rumphorst, K. 최신의학사 1960 最新醫學 Vol.3 No.4

Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

Koo, Bon-Kyoung,Spit, Maureen,Jordens, Ingrid,Low, Teck Y.,Stange, Daniel E.,van de Wetering, Marc,van Es, Johan H.,Mohammed, Shabaz,Heck, Albert J. R.,Maurice, Madelon M.,Clevers, Hans Nature Publishing Group, a division of Macmillan P 2012 Nature Vol.488 No.7413

LGR5<SUP>+</SUP> stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5<SUP>+</SUP> stem cells. Simultaneous deletion of the two genes encoding these proteins in the intestinal epithelium of mice induces rapidly growing adenomas containing high numbers of Paneth and LGR5<SUP>+</SUP> stem cells. In vitro, growth of organoids derived from these adenomas is arrested when Wnt secretion is inhibited, indicating a dependence of the adenoma stem cells on Wnt produced by adenoma Paneth cells. In the HEK293T human cancer cell line, expression of RNF43 blocks Wnt responses and targets surface-expressed frizzled receptors to lysosomes. In the RNF43-mutant colorectal cancer cell line HCT116, reconstitution of RNF43 expression removes its response to exogenous Wnt. We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation.

Tobamovirus Coat Protein CPCg Induces an HR-like Response in Sensitive Tobacco Plants

Patricio Arce-Johnson,Nicole Ehrenfeld,Paola Canon,Claudia Stange,Consuelo Medina 한국분자세포생물학회 2005 Molecules and cells Vol.19 No.3

When inoculated into sensitive tobacco Xanthi-nn plants, the crucifer and garlic-infecting Tobacco mosaic virus (TMV-Cg) induces local necrotic lesions that resemble those seen in the hypersensitive response (HR) of resistant tobacco plants. However, unlike these, tobacco Xanthi-nn plants do not become resistant to infection and the virus spreads systemically causing a severe disease characterized by necrotic lesions throughout the plant. To identify the viral protein that elicits this necrotic response, we used a set of hybrid viruses constructed by combination of TMV-Cg and the tobacco mosaic virus strain U1 (TMV-U1). In this study we present evidence that the coat protein of TMV-Cg (CPCg) is the elicitor of the necrotic response in tobacco Xanthi-nn plants. Local and systemic necrotic lesions induced by TMV-Cg and by the hybrid U1-CPCg -that carries CPCg in a TMV-U1 context- are characterized by cell death and by the presence of autoflorescent phenolic compounds and H2O2, just like the HR lesions. In addition, defense-related genes and detoxifying genes are induced in tobacco Xanthi-nn plants after TMV-Cg and U1-CPCg inoculation. We postulate that in our system, CPCg is recognized by sensitive tobacco plants that mount an incomplete defense response. We call this an HR-like since it is not enough to induce plant resistance.

Notch1 counteracts WNT/β-catenin signaling through chromatin modification in colorectal cancer.

Kim, Hyun-A,Koo, Bon-Kyoung,Cho, Ji-Hoon,Kim, Yoon-Young,Seong, Jinwoo,Chang, Hee Jin,Oh, Young Min,Stange, Daniel E,Park, Jae-Gahb,Hwang, Daehee,Kong, Young-Yun American Society for Clinical Investigation 2012 The Journal of clinical investigation Vol.122 No.9

<P>Crosstalk between the Notch and wingless-type MMTV integration site (WNT) signaling pathways has been investigated for many developmental processes. However, this negative correlation between Notch and WNT/β-catenin signaling activity has been studied primarily in normal developmental and physiological processes in which negative feedback loops for both signaling pathways are intact. We found that Notch1 signaling retained the capability of suppressing the expression of WNT target genes in colorectal cancers even when β-catenin destruction by the adenomatous polyposis coli (APC) complex was disabled. Activation of Notch1 converted high-grade adenoma into low-grade adenoma in an Apcmin mouse colon cancer model and suppressed the expression of WNT target genes in human colorectal cancer cells through epigenetic modification recruiting histone methyltransferase SET domain bifurcated 1 (SETDB1). Extensive microarray analysis of human colorectal cancers also showed a negative correlation between the Notch1 target gene, Notch-regulated ankyrin repeat protein 1 (NRARP), and WNT target genes. Notch is known to be a strong promoter of tumor initiation, but here we uncovered an unexpected suppressive role of Notch1 on WNT/β-catenin target genes involved in colorectal cancer.</P>

Cultural Influences on the Ratings of Behavioral Problems, Emotional Problems, and School Adjustment for Korean and Korean American Adolescents

Woo Jung,Kristin K. Stang,Doreen Ferko,한신일 한국비교교육학회 2012 比較敎育硏究 Vol.22 No.3

This study investigated ratings of social-emotional-behavioral difficulties and school adjustment of Korean adolescents and American born Korean adolescent. Self-report of Korean and American born Korean adolescents were gathered with the Behavior Assessment System for Children (BASC-2). A total of 224 middle and high school students ages 12 to 17 participated in this study. Study of these adolescents provided insight into the effects on Korean American adolescents of being caught between traditional Korean culture and demands for Americanization, as well as the determination of whether there were different anchoring points for child judgments for Korean adolescents versus American born Korean adolescents. The study also provided essential validity evidence for the BASC-2 (SRP), which was needed to inform practitioners who use the system for assessment of Korean and/or Korean American children. There were significant group effects on the SRP scales related to the notion of Korean family collectivism versus western individualism and the inherent conflict in these cultural values was used to discuss the results. Results also suggested that elevated BASC-2 SRP scores may reflect cultural factors rather than psychopathology.

Comparison of Apples with their Parts: Rethinking a Meta-analysis on the Association between Cooking and Uveal Melanoma Risk

Schmidt-Pokrzywniak, Andrea,Stang, Andreas Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Cultural Influences on the Ratings of Behavioral Problems, Emotional Problems, and School Adjustment for Korean and Korean American Adolescents

Woo Jung, Kristin K. Stang, Doreen Ferko, 한신일(Shin-Il Han) 한국비교교육학회 2012 比較敎育硏究 Vol.22 No.3

본 연구는 한국의 청소년과 미국에 거주하는 한국계 청소년에게 발생하는 사회적ㆍ정서적ㆍ행동적 문제와 학교적응문제를 집단 간 비교함으로써, 다양한 문화적 배경에 근거한 미국에 거주하는 한인학생의 이해를 돕는데 목적이 있다. 한국 청소년 136명, 미국에 거주하는 한국계 청소년 88명으로 구성된 총 224명의 학생이 본 연구에 참여하였으며, 이들은 본 연구에 필요한 자기평가보고서를 작성하였다. 자기평가는 ‘Behavior Assessment System for Children (BASC-2)’를 통해 수집되었다. 분석결과, 미국에 거주하는 한국계 학생들이 전통적인 한국문화와 미국문화가 요구하는 상황사이에서 보여주는 심리ㆍ행동적 특징들을 발견할 수 있었다. 또한 한국 청소년과 미국거주 한국계 청소년의 차이를 보여주는 정서 및 행동 특성은 무엇인지를 발견할 수 있었다. 특히 본 연구에서 사용한 BASC-2(SRP) 측정도구가 한국 청소년 및 미국거주의 한인 청소년들의 인식과 정서 그리고 행동을 연구하는데 적합하며 타당하다는 것을 증명한 것은 매우 가치 있는 연구결과라고 할 수 있다. 즉, 이 결과를 통해 BASC-2(SRP) 측정도구가 인간의 정신병리학적 측면보다는 문화적 측면의 특성을 이해하는데 도움을 주고 있다는 것을 발견하게 되었다. 한편, 가족을 중심으로 한 한국의 집단주의적 가치와 미국의 개인주의적 가치는 한국 청소년과 미국에 거주하는 한국계 청소년 간에 나타난 주요한 차이라는 것을 본 연구를 통해 알 수 있었으며, 이러한 문화적 가치 충돌로 나타나는 다양한 이슈들은 본 연구의 토론과 결론에서 심도있게 거론되었다. This study investigated ratings of social-emotional-behavioral difficulties and school adjustment of Korean adolescents and American born Korean adolescent. Self-report of Korean and American born Korean adolescents were gathered with the Behavior Assessment System for Children(BASC-2). A total of 224 middle and high school students ages 12 to 17 participated in this study. Study of these adolescents provided insight into the effects on Korean American adolescents of being caught between traditional Korean culture and demands for Americanization, as well as the determination of whether there were different anchoring points for child judgments for Korean adolescents versus American born Korean adolescents. The study also provided essential validity evidence for the BASC-2 (SRP), which was needed to inform practitioners who use the system for assessment of Korean and/or Korean American children. There were significant group effects on the SRP scales related to the notion of Korean family collectivism versus western individualism and the inherent conflict in these cultural values was used to discuss the results. Results also suggested that elevated BASC-2 SRP scores may reflect cultural factors rather than psychopathology.

Self-assembly of metal-ion-responsive supramolecular coordination complexes and their photophysical properties

He, Zuoli,Li, Meng,Que, Wenxiu,Stang, Peter J. The Royal Society of Chemistry 2017 Dalton transactions Vol.46 No.10

<▼1><P>Herein, we describe the synthesis and characterization of two newly self-assembled supramolecular coordination complexes (SCCs) by using the <I>cis</I>-{Pt(PEt3)2}<SUP>2+</SUP> center and two different kinds of pyridyl-derivatized ligands.</P></▼1><▼2><P>Herein, we describe the synthesis and characterization of two newly self-assembled supramolecular coordination complexes (SCCs) by using the <I>cis</I>-{Pt(PEt3)2}<SUP>2+</SUP> center and two different kinds of pyridyl-derivatized ligands. The photophysical properties of the resulting SCCs in the presence of metal ions revealed that these dipyridyl-containing SCCs hold potential as metal-ion-responsive materials.</P></▼2>