H3K23me2 is a new heterochromatic mark in Caenorhabditis elegans
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE88834 | GEO | 2016/10/17
SECONDARY ACCESSION(S): PRJNA348747
REPOSITORIES: GEO
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2015-05-09 | E-MTAB-3431 | biostudies-arrayexpress
Project description:Chromatin immunoprecipitation (ChIP) experiments were conducted as previously described (Ito et al, 2013) using anti-H3K4me3 (Millipore, #07-473), anti-H3K4me1 (Abcam, #ab8895), or anti-Kdm5C (Iwase et al., 2016). Hippocampi derived from two different animals were pooled together for each sample and two independent biological replicates per condition were sequenced according to manufacturer instructions in a HiSeq2500 apparatus (Illumina, Inc). Information on library preparation method, size of the libraries, and mapping to reference genome can be found in Supplementary Material accompanying the manuscript. ChIP-seq reads were aligned to the mouse genome (Mus_musculus.GRCm.38.83) using bowtie2 (v2.2.9) (Langmead and Salzberg, 2012) and further processed using samtools (v1.3.1) (Li et al., 2009). Peak calling was performed using MACS2 (v2.1.0) (Zhang et al., 2008) with default parameters except for Kdm5c that were as follows: -q 0.01 --nomodel --extsize 131 --broad --broad-cutoff 0.1. Read counts on aligned bam files were performed using Rsubread (v1.22.3) (Liao et al., 2014). Differential peak methylation analysis for H3K4me3 chromatin mark was performed using DESeq2 (v1.10.0) (Love et al., 2014) of the bioconductor suite (Huber et al., 2015) in the R (v3.3) statistical computing platform. For consideration of differentially methylated regions between conditions, we used adjusted p-value < 0.05 as indicated in the manuscript.
2017-08-18 | GSE85873 | GEO
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We found that mammosphere and replating cultures of epithelial (E) cell lines (HP cells and E clones) led to enrichment for mesenchymal (M) signatures characteristic of the mesenchymal cell lines, indicative of an epithelial to mesenchymal transition (EMT), but retainment of E-specific signatures (Grosse-Wilde et al., 2015). This co-expression of E and M signatures was stably maintained between the mammosphere state in suspension and in replated cells, indicating a stable E/M gene expression state by partial EMT in E cell lines, which has been associated with a stem-like state (Grosse-Wilde et al., 2015; Jolly et al., 2014; Lu et al., 2014; Zhang et al., 2014). Interestingly, mammosphere suspension culture of mesenchymal M clones also resulted in co-expression of E and M signatures generated by partial mesenchymal to epithelial transition (MET). However, in stark contrast to E clones and HP cells, immediately upon replating M cell-derived mammospheres to adhesion lost the intermediate E/M state and converted back to stable expression of M signatures indicative of rapid EMT. This suggests that the intermediate state in M cells is very unstable. Together, these replating data suggest that prolonged detachment of epithelial-derived cells leads to loss of expression of E signatures and EMT. Life-threatening macrometastases typically recapitulate the gene expression of the primary tumor, which requires expression of E signatures, while the mesenchymal micrometastases are frequent but not-proliferative and harmless. Since all HMLER cell lines independent of their initial E or M state converged to an M state upon expansion in suspension, our data suggest that induction of EMT in suspended HMLER cells may be one reason for the observed benign non-metastatic character of HMLER cells when used in mouse xenograft experiments, and for their metastatic inefficiency. Our datasets of the replating kinetic may be useful to identify which pathways are involved in the processes enabling the mixed HP population to maintain a stable E/M expression signature and a more stem-like state, which we have identified as caused by cell-cell cooperation between phenotypically different E and M cell-types. By contrast, M cells can only transiently assume this E/M gene expression state, and not generate a stable phenotypic heterogeneity and therefore absence of cooperation between E and M cell-types. Instability of the intermediate stem-like E/M state in M cell-types and rapid conversion to the M state can explain why 1) pure M populations are often phenotypically stable and are not undergoing MET in vitro (Schmidt et al., 2015; Zhang et al., 2014), 2) why pure M populations are less aggressive resulting in less metastases than mixed cooperating E and M cell populations (Ocaña et al., 2012; Tsuji et al., 2008) or 3) why complete EMT results in more benign less metastasizing tumors than incomplete EMT (Tran et al., 2014; Tsai et al., 2012) and finally 4) why expression of M traits in primary tumors are associated with good patient outcomes and less metastases than E signatures (Kim et al., 2011; Mylona et al., 2008; Tan et al., 2014). Dontu, G., Abdallah, W.M., Foley, J.M., Jackson, K.W., Clarke, M.F., Kawamura, M.J., and Wicha, M.S. (2003). In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17, 1253–1270. Elenbaas, B., Spirio, L., Koerner, F., Fleming, M.D., Zimonjic, D.B., Donaher, J.L., Popescu, N.C., Hahn, W.C., and Weinberg, R.A. (2001). Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev 15, 50–65. Grosse-Wilde, A., Fouquier d’Hérouël, A., McIntosh, E., Ertaylan, G., Skupin, A., Kuestner, R.E., del Sol, A., Walters, K.-A., and Huang, S. (2015). Stemness of the hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival. PLOS ONE 10, e0126522. Jolly, M.K., Huang, B., Lu, M., Mani, S.A., Levine, H., and Ben-Jacob, E. (2014). Towards elucidating the connection between epithelial-mesenchymal transitions and stemness. J. R. Soc. Interface R. Soc. 11, 20140962. Kim, H.J., Kim, M.-J., Ahn, S.H., Son, B.H., Kim, S.B., Ahn, J.H., Noh, W.C., and Gong, G. (2011). Different prognostic significance of CD24 and CD44 expression in breast cancer according to hormone receptor status. The Breast 20, 78–85. Lu, M., Jolly, M.K., Onuchic, J., and Ben-Jacob, E. (2014). Toward decoding the principles of cancer metastasis circuits. Cancer Res. 74, 4574–4587. Mylona, E., Giannopoulou, I., Fasomytakis, E., Nomikos, A., Magkou, C., Bakarakos, P., and Nakopoulou, L. (2008). The clinicopathologic and prognostic significance of CD44+/CD24−/low and CD44−/CD24+ tumor cells in invasive breast carcinomas. Hum. Pathol. 39, 1096–1102. Ocaña, O.H., Córcoles, R., Fabra, Á., Moreno-Bueno, G., Acloque, H., Vega, S., Barrallo-Gimeno, A., Cano, A., and Nieto, M.A. (2012). Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1. Cancer Cell 22, 709–724. Schmidt, J.M., Panzilius, E., Bartsch, H.S., Irmler, M., Beckers, J., Kari, V., Linnemann, J.R., Dragoi, D., Hirschi, B., Kloos, U.J., et al. (2015). Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation. Cell Rep. 10, 131–139. Tan, T.Z., Miow, Q.H., Miki, Y., Noda, T., Mori, S., Huang, R.Y.-J., and Thiery, J.P. (2014). Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol. Med. 6, 1279–1293. Tran, H.D., Luitel, K., Kim, M., Zhang, K., Longmore, G.D., and Tran, D.D. (2014). Transient SNAIL1 Expression Is Necessary for Metastatic Competence in Breast Cancer. Cancer Res. 74, 6330–6340. Tsai, J.H., Donaher, J.L., Murphy, D.A., Chau, S., and Yang, J. (2012). Spatiotemporal Regulation of Epithelial-Mesenchymal Transition Is Essential for Squamous Cell Carcinoma Metastasis. Cancer Cell 22, 725–736. Tsuji, T., Ibaragi, S., Shima, K., Hu, M.G., Katsurano, M., Sasaki, A., and Hu, G. -f. (2008). Epithelial-Mesenchymal Transition Induced by Growth Suppressor p12CDK2-AP1 Promotes Tumor Cell Local Invasion but Suppresses Distant Colony Growth. Cancer Res. 68, 10377–10386. Zhang, J., Tian, X.-J., Zhang, H., Teng, Y., Li, R., Bai, F., Elankumaran, S., and Xing, J. (2014). TGF- -induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops. Sci. Signal. 7, ra91–ra91.
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