ACD can configure probes for the various manual and automated assays for INS for RNAscope Assay, or for Basescope Assay compatible for your species of interest.
Cell Stem Cell.
2018 Jan 10
Seino T, Kawasaki S, Shimokawa M, Tamagawa H, Toshimitsu K, Fujii M, Ohta Y, Matano M, Nanki K, Kawasaki K, Takahashi S, Sugimoto S, Iwasaki E, Takagi J, Itoi T, Kitago M, Kitagawa Y, Kanai T, Sato T.
PMID: 29337182 | DOI: 10.1016/j.stem.2017.12.009
Despite recent efforts to dissect the inter-tumor heterogeneity of pancreatic ductal adenocarcinoma (PDAC) by determining prognosis-predictive gene expression signatures for specific subtypes, their functional differences remain elusive. Here, we established a pancreatic tumor organoid library encompassing 39 patient-derived PDACs and identified 3 functional subtypes based on their stem cell niche factor dependencies on Wnt and R-spondin. A Wnt-non-producing subtype required Wnt from cancer-associated fibroblasts, whereas a Wnt-producing subtype autonomously secreted Wnt ligands and an R-spondin-independent subtype grew in the absence of Wnt and R-spondin. Transcriptome analysis of PDAC organoids revealed gene-expression signatures that associated Wnt niche subtypes with GATA6-dependent gene expression subtypes, which were functionally supported by genetic perturbation of GATA6. Furthermore, CRISPR-Cas9-based genome editing of PDAC driver genes (KRAS, CDKN2A, SMAD4, and TP53) demonstrated non-genetic acquisition of Wnt niche independence during pancreas tumorigenesis. Collectively, our results reveal functional heterogeneity of Wnt niche independency in PDAC that is non-genetically formed through tumor progression.
EMBO J.
2018 Jul 23
Maglic D, Schlegelmilch K, Dost AF, Panero R, Dill M, Calogero RA, Camargo FD.
PMID: 30037824 | DOI: 10.15252/embj.201798642
The mammalian Hippo signaling pathway, through its effectors YAP and TAZ, coerces epithelial progenitor cell expansion for appropriate tissue development or regeneration upon damage. Its ability to drive rapid tissue growth explains why many oncogenic events frequently exploit this pathway to promote cancer phenotypes. Indeed, several tumor types including basal cell carcinoma (BCC) show genetic aberrations in the Hippo (or YAP/TAZ) regulators. Here, we uncover that while YAP is dispensable for homeostatic epidermal regeneration, it is required for BCC development. Our clonal analyses further demonstrate that the few emerging Yap-null dysplasia have lower fitness and thus are diminished as they progress to invasive BCC Mechanistically, YAP depletion in BCC tumors leads to effective impairment of the JNK-JUN signaling, a well-established tumor-driving cascade. Importantly, in this context, YAP does not influence canonical Wnt or Hedgehog signaling. Overall, we reveal Hippo signaling as an independent promoter of BCC pathogenesis and thereby a viable target for drug-resistant BCC.
Cell.
2018 Aug 09
Nanki K, Toshimitsu K, Takano A, Fujii M, Shimokawa M, Ohta Y, Matano M, Seino T, Nishikori S, Ishikawa K, Kawasaki K, Togasaki K, Takahashi S, Sukawa Y, Ishida H, Sugimoto S, Kawakubo H, Kim J, Kitagawa Y, Sekine S, Koo BK, Kanai T, Sato T.
PMID: 30096312 | DOI: 10.1016/j.cell.2018.07.027
Recent sequencing analyses have shed light on heterogeneous patterns of genomic aberrations in human gastric cancers (GCs). To explore how individual genetic events translate into cancer phenotypes, we established a biological library consisting of genetically engineered gastric organoids carrying various GC mutations and 37 patient-derived organoid lines, including rare genomically stable GCs. Phenotype analyses of GC organoids revealed divergent genetic and epigenetic routes to gain Wnt and R-spondin niche independency. An unbiased phenotype-based genetic screening identified a significant association between CDH1/TP53 compound mutations and the R-spondin independency that was functionally validated by CRISPR-based knockout. Xenografting of GC organoids further established the feasibility of Wnt-targeting therapy for Wnt-dependent GCs. Our results collectively demonstrate that multifaceted genetic abnormalities render human GCs independent of the stem cell niche and highlight the validity of the genotype-phenotype screening strategy in gaining deeper understanding of human cancers.
Dev Cell. 2018 Dec 19.
2018 Dec 19
Gupta K, Levinsohn J, Linderman G, Chen D, Sun TY, Dong D, Taketo MM, Bosenberg M, Kluger Y, Choate K, Myung P.
PMID: 30595533 | DOI: 10.1016/j.devcel.2018.11.032
Developmental cell
2023 Apr 06
Sun, XL;Chen, ZH;Guo, X;Wang, J;Ge, M;Wong, SZH;Wang, T;Li, S;Yao, M;Johnston, LA;Wu, QF;
PMID: 37054704 | DOI: 10.1016/j.devcel.2023.03.016
Nature biomedical engineering
2023 Jan 12
You, Y;Tian, Y;Yang, Z;Shi, J;Kwak, KJ;Tong, Y;Estania, AP;Cao, J;Hsu, WH;Liu, Y;Chiang, CL;Schrank, BR;Huntoon, K;Lee, D;Li, Z;Zhao, Y;Zhang, H;Gallup, TD;Ha, J;Dong, S;Li, X;Wang, Y;Lu, WJ;Bahrani, E;Lee, LJ;Teng, L;Jiang, W;Lan, F;Kim, BYS;Lee, AS;
PMID: 36635419 | DOI: 10.1038/s41551-022-00989-w
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
2021 Jul 08
Zhang, H;Lin, M;Dong, C;Tang, Y;An, L;Ju, J;Wen, F;Chen, F;Wang, M;Wang, W;Chen, M;Zhao, Y;Li, J;Hou, SX;Lin, X;Hu, L;Bu, W;Wu, D;Li, L;Jiao, S;Zhou, Z;
PMID: 34240584 | DOI: 10.1002/advs.202004850
Bone
2017 Dec 05
Foster BL, Ao M, Salmon CR, Chavez MB, Kolli TN, Tran AB, Chu EY, Kantovitz KR, Yadav M, Narisawa S, Millán JL, Nociti Jr FH, Somerman MJ.
PMID: - | DOI: 10.1016/j.bone.2017.12.004
The periodontal complex is essential for tooth attachment and function and includes the mineralized tissues, cementum and alveolar bone, separated by the unmineralized periodontal ligament (PDL). To gain insights into factors regulating cementum-PDL and bone-PDL borders and protecting against ectopic calcification within the PDL, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock-out (Ank−/−) mice, featuring reduced PPi, rapid cementogenesis, and excessive acellular cementum. Using this approach, we identified the matrix protein osteopontin (Spp1/OPN) as an elevated factor of interest in Ank−/− mouse molar PDL. We studied the role of OPN in dental and periodontal development and function. During tooth development in wild-type (WT) mice, Spp1 mRNA was transiently expressed by cementoblasts and strongly by alveolar bone osteoblasts. Developmental analysis from 14 to 240 days postnatal (dpn) indicated normal histological structures in Spp1−/− comparable to WT control mice. Microcomputed tomography (micro-CT) analysis at 30 and 90 dpn revealed significantly increased volumes and tissue mineral densities of Spp1−/− mouse dentin and alveolar bone, while pulp and PDL volumes were decreased and tissue densities were increased. However, acellular cementum growth was unaltered in Spp1−/− mice. Quantitative PCR of periodontal-derived mRNA failed to identify potential local compensators influencing cementum in Spp1−/− vs. WT mice at 26 dpn. We genetically deleted Spp1 on the Ank−/− mouse background to determine whether increased Spp1/OPN was regulating periodontal tissues when the PDL space is challenged by hypercementosis in Ank−/− mice. Ank−/−; Spp1−/−double deficient mice did not exhibit greater hypercementosis than that in Ank−/− mice. Based on these data, we conclude that OPN has a non-redundant role regulating formation and mineralization of dentin and bone, influences tissue properties of PDL and pulp, but does not control acellular cementum apposition. These findings may inform therapies targeted at controlling soft tissue calcification.
SSRN Electronic Journal
2022 Oct 13
Christiansen, P;Andreasen, C;Laursen, K;Delaisse, J;Andersen, T;
| DOI: 10.2139/ssrn.4224428
Investigative Ophthalmology & Visual Science
2022 Jan 01
Zhu, X;Xu, M;Grachtchouk, M;
Nat Cell Biol.
2017 Apr 10
Turco MY, Gardner L, Hughes J, Cindrova-Davies T, Gomez MJ, Farrell L, Hollinshead M, Marsh SG, Brosens JJ, Critchley HO, Simons BD, Hemberger M, Koo BK, Moffett A, Burton GJ.
PMID: 28394884 | DOI: 10.1038/ncb3516
In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.
Cell stem cell
2023 Mar 14
You, Z;Wang, L;He, H;Wu, Z;Zhang, X;Xue, S;Xu, P;Hong, Y;Xiong, M;Wei, W;Chen, Y;
PMID: 36933556 | DOI: 10.1016/j.stem.2023.02.007
Description | ||
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sense Example: Hs-LAG3-sense | Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe. | |
Intron# Example: Mm-Htt-intron2 | Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection | |
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G) | A mixture of multiple probe sets targeting multiple genes or transcripts | |
No-XSp Example: Hs-PDGFB-No-XMm | Does not cross detect with the species (Sp) | |
XSp Example: Rn-Pde9a-XMm | designed to cross detect with the species (Sp) | |
O# Example: Mm-Islr-O1 | Alternative design targeting different regions of the same transcript or isoforms | |
CDS Example: Hs-SLC31A-CDS | Probe targets the protein-coding sequence only | |
EnEm | Probe targets exons n and m | |
En-Em | Probe targets region from exon n to exon m | |
Retired Nomenclature | ||
tvn Example: Hs-LEPR-tv1 | Designed to target transcript variant n | |
ORF Example: Hs-ACVRL1-ORF | Probe targets open reading frame | |
UTR Example: Hs-HTT-UTR-C3 | Probe targets the untranslated region (non-protein-coding region) only | |
5UTR Example: Hs-GNRHR-5UTR | Probe targets the 5' untranslated region only | |
3UTR Example: Rn-Npy1r-3UTR | Probe targets the 3' untranslated region only | |
Pan Example: Pool | A mixture of multiple probe sets targeting multiple genes or transcripts |
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