A dynamic in vitro model of Down Syndrome neurogenesis with Trisomy 21 gene dosage correction
Data files
May 17, 2024 version files 107.33 MB
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ElapsedHours-1.csv
150 B
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fig1c_ipsc_if_fish.csv
2.60 KB
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fig6a_neural_h2a_xist.csv
6.04 KB
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fig6b_neural_lineage_commitment.csv
6.30 KB
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fig7bleft_neural_post_dapt_edu.csv
1.60 KB
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fig7bright_neural_post_dapt_edu_xist.csv
1.21 KB
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fig7d_terminal_neurons_astrocytes_at1012wks.csv
10.46 KB
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Forebrain_cell_data.csv
82.04 MB
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inter_Generated_Crops_2021-11-11-1.csv
6.56 MB
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Interneurons_cell_data.csv
18.70 MB
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platelayoutInterneurons-1.csv
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README.md
5.82 KB
Abstract
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 efficiently represses genes even after terminal differentiation, which will empower the exploration of cell type-specific T21 phenotypes that remain responsive to chr21 dosage.
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 cell lines that the cells being imaged belong to.
- genotype - Whether the cell line being imaged is euploid, trisomic (T21), or has the transgene (T21-XIST).
- DiffRound - Round of neural differentiation.
- MAP2_positive_nuclei - The number of nuclei that stained positive for MAP2.
- s100b_positive_nuclei - The number of nuclei that stained positive for s100b.
- edu_positive - The number of nuclei that stained positive for EdU.
- only_xist_positive - The number of nuclei that were only positive for XIST (and negative for EdU) in slides that were co-stained for EdU IF and XIST FISH.
- only_edu_positive - The number of nuclei that were only positive for EdU (and negative for XIST) in slides that were co-stained for EdU IF and XIST FISH.
- double_positive - The number of nuclei that were positive for both XIST and EdU in slides that were co-stained for EdU IF and XIST FISH.
Column Header Definitions for GEDI data:
| cell_data_column_name | Column_Description |
|---|---|
| ObjectCount | number of cells per well_timepoint in GFP channel |
| ObjectLabelsFound | well_timepoint neuron identity |
| MeasurementTag | Fluorescence channel |
| BlobArea | Size of neuron mask (in micrometer-squared) |
| BlobPerimeter | neuron mask perimeter (in micrometers) |
| Radius | neuron radius (in micrometers) |
| BlobCentroidX | neuron centroid location |
| BlobCentroidY | neuron centroid location |
| BlobCentroidX_RefIntWeighted | neuron mask centroid location weighted for intensity |
| BlobCentroidY_RefIntWeighted | neuron mask centroid location weighted for intensity |
| BlobCircularity | neuron circularity |
| Spread | neuron fluorescence spread |
| Convexity | neuron mask convexity |
| PixelIntensityMaximum | neuron mask max |
| PixelIntensityMinimum | neuron mask min |
| PixelIntensityMean | neuron mask mean |
| PixelIntensityVariance | neuron mask variance |
| PixelIntensityStdDev | neuron mask std |
| PixelIntensity1Percentile | neuron mask 1st percentile fluorescence |
| PixelIntensity5Percentile | neuron mask 5th percentile fluorescence |
| PixelIntensity10Percentile | neuron mask 10th percentile fluorescence |
| PixelIntensity25Percentile | neuron mask 25th percentile fluorescence |
| PixelIntensity50Percentile | neuron mask 50th percentile fluorescence |
| PixelIntensity75Percentile | neuron mask 75th percentile fluorescence |
| PixelIntensity90Percentile | neuron mask 90th percentile fluorescence |
| PixelIntensity95Percentile | neuron mask 95th percentile fluorescence |
| PixelIntensity99Percentile | neuron mask 99th percentile fluorescence |
| PixelIntensitySkewness | neuron mask skew |
| PixelIntensityKurtosis | neuron mask kurtosis |
| PixelIntensityInterquartileRange | neuron mask iqr |
| PixelIntensityTotal | neuron mask total intensity |
| Sci_PlateID | experiment name |
| Sci_WellID | well |
| RowID | well row |
| ColumnID | well column |
| Timepoint | timepoint |
| ElapsedHours | NA |
Sharing/Access information
Additional sequencing and sample data are available through dbGaP (phs002397.v1.p1).
Code/Software
The accompanying code for this paper is also present at: