Epigenomic heterogeneity and spatial organization during human reprogramming

Li, Terence W.; Langerman, Justin; Liu, Cuining; Sun, Yu; Balliu, Brunilda; Ernst, Jason; Luo, Chongyuan; Plath, Kathrin

Preprint in preparation · IGVF Consortium · UCLA

Epigenomic heterogeneity and spatial organization during human reprogramming

Terence W. Li^1,2,3,*, Justin Langerman^4,*, Cuining Liu^1,3,*, Yu Sun^4,*, Mohammad S. Baig^1,5, Gianna Kim¹, Jingyuan Fu^4,6, Rayyan Irfan Ghoor¹, Yi Zhang¹, Zach Von Behren¹, Min Jen Tsai¹, Malina Elena Cantemir¹, Kevin D. Abuhanna^1,5, Edward Chen¹, Jon Paino⁶, Gideon Shaked⁴, Lily Zhao⁴, Lisa Barooah⁴, Amy Sun⁴, Andrea Garcia Angulo⁴, Alexander Lee⁴, Sophia Peavy⁴, Eleazar Eskin^1,2,6, Noah Zaitlen^1,2,7, Brunilda Balliu^2,8,9,†, Jason Ernst^2,4,6,†, Chongyuan Luo^1,†, Kathrin Plath^4,†

Affiliations · ^*co-first authors · ^†co-corresponding authors

Department of Human Genetics, David Geffen School of Medicine, UCLA
Department of Computational Medicine, David Geffen School of Medicine, UCLA
Bioinformatics Interdepartmental Program, UCLA
Department of Biological Chemistry, David Geffen School of Medicine, UCLA
Genetics and Genomics Graduate Program, UCLA
Computer Science Department, Henry Samueli School of Engineering and Applied Science, UCLA
Department of Neurology, David Geffen School of Medicine, UCLA
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA
Department of Biostatistics, Fielding School of Public Health, UCLA

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Summary

Fibroblasts from four individuals were reprogrammed to induced pluripotent stem cells and sampled at up to 11 time points. Cells were profiled for single-nucleus gene expression and chromatin accessibility (10x Multiome), DNA methylation with transcriptome (snMCT-seq), and DNA methylation with 3D genome organization (snM3C-seq). Highly multiplexed spatial transcriptomics (CosMx) was performed on selected time points, and each donor was whole-genome sequenced.

Data

Raw/processed data is deposited on the IGVF portal and publicly released. The five principal analysis sets below are post-QC, and we provide download links for all raw/intermediate files used to generate them.

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