Wnt-mediated mechanisms that regulate somatic cell reprogramming and pluripotency.


The Cosma lab discovered that activation of the Wnt/beta-catenin signalling pathway enhances cell-fusion-mediated reprogramming of a variety of somatic cells (Lluis et al., Cell Stem Cell 2008, Stem Cells 2010). Furthermore, the lab proposed that Tcf3 functions as a repressor of the reprogramming potential of somatic cells by largely modulating epigenome modifications during the reprogramming process (Lluis et al., PNAS 2011; Ombrato et al., Cell Cycle 2012). Further key observations showed that fluctuations of the Wnt signalling pathway control the maintenance of mESC pluripotency and are essential for reprogramming (Marucci et al. Cell Reports 2014; Aulicino et al. Stem Cell Reports 2014; Aulicino et al. Stem Cell Reports 2020). The lab also showed that Wnt activity regulates cell cycle in mESCs and safeguards mESCs epigenetic stability (De Jaime-Soguero et al, Plos Genetics 2017; Theka et al. Scientific Reports 2019). Recently In collaboration with Andrea Califano (Columbia University, USA) we used reverse engineering algorithms to identify “Master Regulators” (MRs) of reprogramming and pluripotency. We identified BAZ2B as an MR able to convert human hematopoietic progenitors into hematopoietic stem cells enhancing their long-term clonogenicity and stemness after transplantation (Arumugam et al. Cell Reports, 2020).