Fig. 4.

Identifying direct effects of Trisomy 21 on human cell types and gene pathways. Surprisingly little is known as to what human cell types are directly (or indirectly) impacted by trisomy 21, nor is it known when deficits arise. A system to induce silencing of one Chr21 (by XIST RNA) in DS patient-derived stem cells provides a tightly controlled approach to identify if there are direct effects of chr21 over-expression on various human cell types, and also provides a novel means to test when changes arise and may be reversible. Note, this approach compares identical populations of cells with and without dox induction and, therefore, avoids confounding variation that often arises between isogenic iPS cell lines. Figures created with Biorender.com