E-mail: a.c.raposo@tecnico.ulisboa.pt
MSc in Molecular Biology and Genetics, Faculty of Sciences, University of Lisbon, Portugal, 2011
BSc in Biology, Instituto Superior de Agronomia, University of Lisbon, Portugal, 2009
Human induced pluripotent stem cells (hiPSCs) are a powerful model system for disease modelling, drug screening and regenerative medicine. However, current hiPSCs have recurrent epigenetic defects which might impacts in their downstream applications. One remarkable example occurs at the level of the X-chromosome inactivation (XCI) in female hiPSCs. XCI is an epigenetic process occurring in female mammalian cells which results in the transcriptional silencing of genes on one of the two X chromosomes to ensure dosage compensation between the sexes. However, prolonged culture of hiPSCs often leads to partial reactivation of the Xi, a process known as XCI erosion. This process is initiated by the loss of XIST long non-coding RNA expression, the master regulator of XCI, and is characterized by an irreversible reactivation of some, but not all, X-linked genes.
My work is focused on the effects of erosion for hiPSCs downstream applications. I am studying in detail the reactivation signature of XCI erosion by RNAseq analysis with allele-resolution for a subset of hiPSCs lines. I am also determining the consequences of the erosion in the differentiation of hiPSCs by performing 3D cardiac differentiation.
Silva, T.P., Pereira, C.A., Raposo, A.C., Oliveira, A.R., Arez, M., Cabral, J.M.S., Milagre, I., Carmo-Fonseca, M., da Rocha, S.T. Generation and characterization of induced pluripotent stem heterozygous for the Portuguese BRCA2 founder mutation. Stem Cell Res 53:102364 (2021).
Silva, T.P., Pereira, C.A., Oliveira, A.R., Raposo, A.C., Arez, M., Cabral, J.M.S., Milagre, I., Carmo-Fonseca, M., da Rocha, S.T. Generation and characterization of induced pluripotent stem cells from a family carrying the BRCA1 mutation c.3612delA. Stem Cell Res 52:102242 (2021).
Tjalsma, S.J.D., Hori, M., Sato, Y., Bousard, A., Ohi, A., Raposo, A.C., Roensch, J., Le Saux, A., Nogami, J., Maehara, K., Kujirai, T., Handa, T., Bagés-Arnal, S., Ohkawa, Y., Kurumizaka, H., da Rocha, S.T., Żylicz, J.J., Kimura, H., Heard, E. H4K20me1 and H3K27me3 are concurrently loaded onto the inactive X chromosome but dispensable for inducing gene silencing. EMBO Rep 22:e51989 (2021).
Bousard, A., Raposo, A.C., Żylicz, J.J., Picard, C., Pires, V.B., Qi, Y., Gil, C., Syx, L., Chang, H.Y., Heard, E., da Rocha, S.T. The role of Xist-mediated Polycomb recruitment in the initiation of X-chromosome inactivation. Stem Cell Res 20:e48019 (2019).