This study investigates chromatin architecture reorganization during stem cell differentiation, using genome-wide chromatin interaction maps in human embryonic stem cells (hESCs) and four derived lineages: Mesendoderm (ME), Mesenchymal Stem Cells (MSC), Neural Progenitor Cells (NPC), and Trophoblast-Like Cells (TB). The research reveals extensive chromatin reorganization during lineage specification, with topological domain boundaries remaining intact but interactions within and between domains changing dramatically, altering 36% of active and inactive chromosomal compartments. Integration of chromatin interaction maps with haplotype-resolved epigenome and transcriptome datasets shows widespread allelic bias in gene expression correlated with allele-biased chromatin states of linked promoters and distal enhancers. The study also explores domain-level chromatin dynamics, finding that while TADs remain stable between cell types, numerous changes in chromatin structure occur within domains. These changes are correlated with active marks such as DHS, H3K27ac, and CTCF binding, and with repressive chromatin modifications such as H3K27me3 and H3K9me3. TADs with increased intra-domain interaction frequency tend to shift from the B to A compartments, while those with decreased interaction frequency shift from A to B. Chromatin state and dynamic interactions are analyzed, revealing that chromatin state features provide information on changes in interaction frequency, with H3K4me1 density being the most important feature in predicting changes in long-range chromatin interactions. Allele-specific chromatin organization is also examined, showing that homologous chromosomes have highly similar A/B compartment patterns, with only 0.6-2.3% of the genome having different A/B compartments between alleles in any given cell type. Allelic imbalances in gene expression are observed, with 1,787 genes showing allelic bias in gene expression in one or more lineages studied here, representing ~24% of all testable genes. These results suggest that most allelic gene expression is due to mechanisms other than genomic imprinting, with allelic bias in activity of cis-regulatory elements near these genes being a possible regulatory mechanism. The study also identifies allele-biased enhancers and shows that allele-biased enhancer activity is a possible mechanism underlying allele-biased gene expression. These findings provide a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.This study investigates chromatin architecture reorganization during stem cell differentiation, using genome-wide chromatin interaction maps in human embryonic stem cells (hESCs) and four derived lineages: Mesendoderm (ME), Mesenchymal Stem Cells (MSC), Neural Progenitor Cells (NPC), and Trophoblast-Like Cells (TB). The research reveals extensive chromatin reorganization during lineage specification, with topological domain boundaries remaining intact but interactions within and between domains changing dramatically, altering 36% of active and inactive chromosomal compartments. Integration of chromatin interaction maps with haplotype-resolved epigenome and transcriptome datasets shows widespread allelic bias in gene expression correlated with allele-biased chromatin states of linked promoters and distal enhancers. The study also explores domain-level chromatin dynamics, finding that while TADs remain stable between cell types, numerous changes in chromatin structure occur within domains. These changes are correlated with active marks such as DHS, H3K27ac, and CTCF binding, and with repressive chromatin modifications such as H3K27me3 and H3K9me3. TADs with increased intra-domain interaction frequency tend to shift from the B to A compartments, while those with decreased interaction frequency shift from A to B. Chromatin state and dynamic interactions are analyzed, revealing that chromatin state features provide information on changes in interaction frequency, with H3K4me1 density being the most important feature in predicting changes in long-range chromatin interactions. Allele-specific chromatin organization is also examined, showing that homologous chromosomes have highly similar A/B compartment patterns, with only 0.6-2.3% of the genome having different A/B compartments between alleles in any given cell type. Allelic imbalances in gene expression are observed, with 1,787 genes showing allelic bias in gene expression in one or more lineages studied here, representing ~24% of all testable genes. These results suggest that most allelic gene expression is due to mechanisms other than genomic imprinting, with allelic bias in activity of cis-regulatory elements near these genes being a possible regulatory mechanism. The study also identifies allele-biased enhancers and shows that allele-biased enhancer activity is a possible mechanism underlying allele-biased gene expression. These findings provide a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.