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).