LGA_HSPC_PAPER

This repository contains all scripts used to perform the analyses described in the manuscript entitled: "Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates" from Pelletier et al., 2022 (doi: 10.3390/ijms23137323).

Scripts were executed using the following Docker images stored on Docker Hub:

• umr1283/stat:R403
• umr1283/stat:4.0.5

Data sharing statement: see manuscript.

Analyses:

• Optimized methylation gene set analysis reveals association between LGA DNA hypermethylation and stem cell differentiation pathways
  1. 01-lga_vs_ctrl_limma_DMCs_analysis.R
  2. 02-gene_score_calculation_and_validation.R
  3. 03-pathway_analysis.R
• Single-cell transcriptomic analysis confirms alteration of hyper-methylated genes in pathways regulating stem cell differentiation among LGA HSCs
  1. 04-make_hematomap.R
  2. 05-integr_singlecell_cbps.R
  3. 06-LGA_vs_Ctrl_RNA.R
• DNA methylation changes occurs in HSCs and DEGs associated open chromatin regions
  1. 07-DMCs_ATAC_integr.R
  2. 08-chromatin_change_LGA_vs_Ctrl.R
• EGR1, KLF2 and KLF4 are key upstream regulators influenced by early epigenetic programming in LGA
  1. 09-SCENIC.R
  2. 10-regulons_enrichment_genescore.R
  3. 10A-motif_analysis.R
• Multimodal co-regulatory network recapitulating TF-gene interactions influenced by early epigenetic programming in LGA
  1. 11-GRN_regulons.R
  2. 12-GRN_final.R
• In vitro analysis confirms the alteration of HSPCs differentiation capacities in LGA
  1. 13-Pseudotime.R
  2. 14-RNA_velocity.R
  3. 15-figures_epi_response.R

Figures and statistical tests: 15-figures_epi_response.R