Identification of epigenomic signatures that define open chromatin regulatory networks associated with mesenchymal differentiation from human pluripotent stem cells

• Grant number: 14/02245-3
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2014
• Effective date (End): June 30, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: Houtan Noushmehr
• Grantee: Tathiane Maistro Malta Pereira
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 15/07925-5 - Open source software statistical tools to aid in analyzing and integrating large cancer epigenomic datasets in order to decipher and understand regulatory networks, AP.JP
• Associated scholarship(s): 16/01975-3 - Defining stem cell epigenomic signatures in 33 different tumor types across 9000+ tumor samples, BE.EP.PD

Abstract

As pluripotent stem cells become important in clinical application to treat certain complex diseases; efficient, reliable, and reproducible protocols of differentiation must be established, in order to obtain functional and terminally differentiated cells, with no risk of tumor formation. Recent studies show phenotypic, molecular and differentiation propensity variability among different embryonic stem cells (ESC) and induced pluripotent stem cells (iPS) cell lines. One of the obstacles for the differentiation of pluripotent cells is the correct epigenetic remodeling that may occur. In this way, epigenomic mapping of pluripotent stem cells can contribute to the control of pluripotency and the differentiation processes in cell lineages that are important for therapeutic application. In this context, this project aims to map epigenomic signatures (transcriptome, methylome, and identification of active regulatory regions) of human pluripotent cell lines (ESC and iPS) generated from Brazilian individuals, using next-generation sequencing. This approach will provide a complete set of data capable of characterizing Brazilian cell lines as a basis for future investigations of these cells for use in cell therapy studies involving genetic diseases and cancer. Moreover, this study aims to map the epigenetic dynamic due to commitment of pluripotent stem cells in response to mesenchymal differentiation. We also aim to compare the efficiency of pluripotent differentiation among different cell lines and correlate with epigenetic changes resulting from the process. The prediction of an epigenetic signature that favors mesenchymal differentiation would be of great importance to assist in choosing the best cell type to be used for therapeutic purposes.

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MALTA, TATHIANE M.; DE SOUZA, CAMILA F.; SABEDOT, THAIS S.; SILVA, TIAGO C.; MOSELLA, MARITZA S.; KALKANIS, STEVEN N.; SNYDER, JAMES; CASTRO, ANA VALERIA B.; NOUSHMEHR, HOUTAN. Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications. NEURO-ONCOLOGY, v. 20, n. 5, p. 608-620, MAY 2018. Web of Science Citations: 19.

DE SOUZA, CAMILA FERREIRA; SABEDOT, THAIS S.; MALTA, TATHIANE M.; STETSON, LINDSAY; MOROZOVA, OLENA; SOKOLOV, ARTEM; LAIRD, PETER W.; WIZNEROWICZ, MACIEJ; IAVARONE, ANTONIO; SNYDER, JAMES; DECARVALHO, ANA; SANBORN, ZACHARY; MCDONALD, KERRIE L.; FRIEDMAN, WILLIAM A.; TIRAPELLI, DANIELA; POISSON, LAILA; MIKKELSEN, TOM; CARLOTTI, JR., CARLOS G.; KALKANIS, STEVEN; ZENKLUSEN, JEAN; SALAMA, SOFIE R.; BARNHOLTZ-SLOAN, JILL S.; NOUSHMEHR, HOUTAN. A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence. CELL REPORTS, v. 23, n. 2, p. 637-651, APR 10 2018. Web of Science Citations: 21.

MALTA, TATHIANE M.; SOKOLOV, ARTEM; GENTLES, ANDREW J.; BURZYKOWSKI, TOMASZ; POISSON, LAILA; WEINSTEIN, JOHN N.; KAMINSKA, BOZENA; HUELSKEN, JOERG; OMBERG, LARSSON; GEVAERT, OLIVIER; COLAPRICO, ANTONIO; CZERWINSKA, PATRYCJA; MAZUREK, SYLWIA; MISHRA, LOPA; HEYN, HOLGER; KRASNITZ, ALEX; GODWIN, ANDREW K.; LAZAR, ALEXANDER J.; STUART, JOSHUA M.; HOADLEY, KATHERINE A.; LAIRD, PETER W.; NOUSHMEHR, HOUTAN; WIZNEROWICZ, MACIEJ; NETWORK, CANCER GENOME ATLAS RES. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation. Cell, v. 173, n. 2, p. 338+, APR 5 2018. Web of Science Citations: 92.

COLAPRICO, ANTONIO; SILVA, TIAGO C.; OLSEN, CATHARINA; GAROFANO, LUCIANO; CAVA, CLAUDIA; GAROLINI, DAVIDE; SABEDOT, THAIS S.; MALTA, TATHIANE M.; PAGNOTTA, STEFANO M.; CASTIGLIONI, ISABELLA; CECCARELLI, MICHELE; BONTEMPI, GIANLUCA; NOUSHMEHR, HOUTAN. TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Research, v. 44, n. 8 MAY 5 2016. Web of Science Citations: 151.

CECCARELLI, MICHELE; BARTHEL, FLORIS P.; MALTA, TATHIANE M.; SABEDOT, THAIS S.; SALAMA, SOFIE R.; MURRAY, BRADLEY A.; MOROZOVA, OLENA; NEWTON, YULIA; RADENBAUGH, AMIE; PAGNOTTA, STEFANO M.; ANJUM, SAMREEN; WANG, JIGUANG; MANYAM, GANIRAJU; ZOPPOLI, PIETRO; LING, SHIYUN; RAO, ARJUN A.; GRIFFORD, MIA; CHERNIACK, ANDREW D.; ZHANG, HAILEI; POISSON, LAILA; CARLOTTI, JR., CARLOS GILBERTO; TIRAPELLI, DANIELA PRETTI DA CUNHA; RAO, ARVIND; MIKKELSEN, TOM; LAU, CHING C.; YUNG, W. K. ALFRED; RABADAN, RAUL; HUSE, JASON; BRAT, DANIEL J.; LEHMAN, NORMAN L.; BARNHOLTZ-SLOAN, JILL S.; ZHENG, SIYUAN; HESS, KENNETH; RAO, GANESH; MEYERSON, MATTHEW; BEROUKHIM, RAMEEN; COOPER, LEE; AKBANI, REHAN; WRENSCH, MARGARET; HAUSSLER, DAVID; ALDAPE, KENNETH D.; LAIRD, PETER W.; GUTMANN, DAVID H.; NOUSHMEHR, HOUTAN; IAVARONE, ANTONIO; VERHAAK, ROEL G. W.; NETWORK, TCGA RES. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell, v. 164, n. 3, p. 550-563, JAN 28 2016. Web of Science Citations: 464.