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by Keyword: Epigenetic


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Xia, Yun, Montserrat, Nuria, Campistol, Josep M., Izpisua Belmonte, Juan Carlos, Remuzzi, Giuseppe, Williams, David F., (2017). Lineage reprogramming toward kidney regeneration Kidney Transplantation, Bioengineering and Regeneration (ed. Orlando, G., Remuzzi, Giuseppe, Williams, David F.), Academic Press (London, UK) , 1167-1175

We have known for decades that it is possible to switch the phenotype of one somatic cell type into another. Such epigenetic rewiring processes can be artificially managed and even reversed by using a defined set of transcription factors. Lineage reprogramming is very often defined as a process of converting one cell type into another without going through a pluripotent state, providing great promise for regenerative medicine. However, the identification of key transcription factors for lineage reprogramming is limited, due to the exhaustive and expensive experimental processes. Accumulating knowledge of genetic and epigenetic regulatory networks that are critical for defining a specific lineage provides unprecedented opportunities to model and predict pioneering factors that may drive directional lineage reprogramming to obtain the desired cell type.

Keywords: Reprogramming, Pluripotency, Differentiation, Lineage specification, Epigenetic regulatory network, Regeneration


Eguizabal, C., Herrera, L., De Oñate, L., Montserrat, N., Hajkova, P., Izpisua Belmonte, J. C., (2016). Characterization of the epigenetic changes during human gonadal primordial germ cells reprogramming Stem Cells , 34, (9), 2418-2428

Abstract: Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads.

Keywords: Epigenetic, Human primordial germ cells, Reprograming