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Spatial genome re-organization between fetal and adult hematopoietic stem cells [Capture-C]

ABSTRACT: Fetal hematopoietic stem cells (HSCs) undergo a developmental switch to become adult HSCs. The functional properties of the HSCs change dramatically during this switch, including their cycling behavior, hematopoietic lineage outputs and proliferation rate. The relationship between three-dimensional (3D) genome organization, epigenomic state, and transcriptome is poorly understood during this critical developmental transition. Here we conduct a comprehensive survey of the 3D genome, epigenome and transcriptome of fetal and adult HSCs in mouse. We found that chromosomal compartments and topologically associating domains (TAD) are largely conserved between fetal and adult HSCs. However, there is a global trend of increased compartmentalization and TAD boundary strength. In contrast, dynamics of intra-TAD chromatin interactions is much higher, involving thousands? of gene promoters and distal enhancers. Such dynamic interactions target genes involved in cell cycle, metabolism, and hematopoiesis. These developmental-stage-specific enhancer-promoter interactions appear to be mediated by different sets of transcription factors in fetal and adult HSCs, such as TCF3, MAFB, TCF7L2, and NR3C1. Loss of function studies of TCF3 confirms the role of TCF3 in mediating condition-specific enhancer looping and gene regulation in fetal HSCs. In summary, our data suggest that the fetal-to-adult transition is accompanied by extensive changes in intra-TAD chromatin interactions that target genes underlying the phenotypic differences between fetal and adult HSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE119339 | GEO | 2019/12/16

REPOSITORIES: GEO

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