A dynamic in vitro model of Down Syndrome neurogenesis with Trisomy 21 gene dosage correction

Excess gene dosage from chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental as well as acute phenotypes in terminal cell types. Which phenotypes remain amenable to intervention after development is unknown. To address this question in a model of DS neurogenesis, we derived trisomy 21 (T21) human induced pluripotent stem cells (iPSCs) alongside otherwise isogenic euploid controls from mosaic DS fibroblasts, and equipped one chr21 copy with an inducible XIST transgene. Monoallelic chr21 silencing by XIST is near-complete and irreversible in iPSCs. Differential expression reveals that T21 neural lineages and iPSCs share suppressed translation and mitochondrial pathways and activate cellular stress responses. When XIST is induced before the neural progenitor stage, T21 dosage correction suppresses a pronounced skew towards astrogenesis in neural differentiation. Because our transgene remains inducible in post-mitotic T21 neurons and astrocytes, we demonstrate that XIST e..., , , # A dynamic in vitro model of Down Syndrome neurogenesis with Trisomy 21 gene dosage correction

[https://doi.org/10.5061/dryad.8kprr4xvc](https://doi.org/10.5061/dryad.8kprr4xvc)

Here is the data for the image quantification presented in the article in Figures 1C, 6A, 6B, 7B, and 7D.

## Description of the data and file structure

The data is presented as CSVs for each corresponding figure panel. The column headers are defined as follows:

* image - an image ID number
* clone - The T21XIST clone being imaged
* dox - Status of doxycycline treatment, or when dox treatment was started.
* timepoint - For iPSCs, timepoint refers to sample collection timepoint in weeks.
* target - The marker being counted (for IF this is either H3K27me3 or H2AK119ub staining, and for FISH it is XIST staining).
* positive_nuclei - The number of nuclei that are positive for the corresponding target on that image.
* total_nuclei - The total number of nuclei counted on that image.
* Line - The c...