Individuals increasingly participate in online platforms where they copy, share and form they opinions. Social interactions in these platforms are mediated by digital institutions, which dictate algorithms that in turn affect how users form and evolve their opinions. In this work, we examine the conditions under which convergence on shared opinions can be obtained in a social network where connected agents repeatedly update their normalised cardinal preferences (i.e. value systems) under the influence of a non-constant reflexive signal (i.e. institution) that aggregates populations' information using a proportional representation rule. We analyse the impact of institutions that aggregate (i) expressed opinions (i.e. opinion-aggregation institutions), and (ii) cardinal preferences (i.e. value-aggregation institutions). We find that, in certain regions of the parameter space, moderate institutional influence can lead to moderate consensus and strong institutional influence can lead to polarisation. In our randomised network, local coordination alone in the total absence of institutions does not lead to convergence on shared opinions, but very low levels of institutional influence are sufficient to generate a feedback loop that favours global conventions. We also show that opinion-aggregation may act as a catalyst for value change and convergence. When applied to digital institutions, we show that the best mechanism to avoid extremism is to increase the initial diversity of the value systems in the population.

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by mutations in the gene encoding the WAS protein (WASp). Here, induced pluripotent stem cells (iPSCs) were derived from a WAS patient (WAS-iPSC) and the endogenous chromosomal WAS locus was targeted with a wtWAS-2A-eGFP transgene using zinc finger nucleases (ZFNs) to generate corrected WAS-iPSC (cWAS-iPSC). WASp and GFP were first expressed in the earliest CD34(+)CD43(+)CD45(-) hematopoietic precursor cells and later in all hematopoietic lineages examined. Whereas differentiation to non-lymphoid lineages was readily obtained from WAS-iPSCs, in vitro T lymphopoiesis from WAS-iPSC was deficient with few CD4(+)CD8(+) double-positive and mature CD3(+) T cells obtained. T cell differentiation was restored for cWAS-iPSCs. Similarly, defects in natural killer cell differentiation and function were restored on targeted correction of the WAS locus. These results demonstrate that the defects exhibited by WAS-iPSC-derived lymphoid cells were fully corrected and suggests the potential therapeutic use of gene-corrected WAS-iPSCs.

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by mutations in the gene encoding the WAS protein (WASp). Here, induced pluripotent stem cells (iPSCs) were derived from a WAS patient (WAS-iPSC) and the endogenous chromosomal WAS locus was targeted with a wtWAS-2A-eGFP transgene using zinc finger nucleases (ZFNs) to generate corrected WAS-iPSC (cWAS-iPSC). WASp and GFP were first expressed in the earliest CD34(+)CD43(+)CD45(-) hematopoietic precursor cells and later in all hematopoietic lineages examined. Whereas differentiation to non-lymphoid lineages was readily obtained from WAS-iPSCs, in vitro T lymphopoiesis from WAS-iPSC was deficient with few CD4(+)CD8(+) double-positive and mature CD3(+) T cells obtained. T cell differentiation was restored for cWAS-iPSCs. Similarly, defects in natural killer cell differentiation and function were restored on targeted correction of the WAS locus. These results demonstrate that the defects exhibited by WAS-iPSC-derived lymphoid cells were fully corrected and suggests the potential therapeutic use of gene-corrected WAS-iPSCs.