Spatial Genome Re-organization between Fetal and Adult Hematopoietic Stem Cells

Cell Rep. 2019 Dec 17;29(12):4200-4211.e7. doi: 10.1016/j.celrep.2019.11.065.


Fetal hematopoietic stem cells (HSCs) undergo a developmental switch to become adult HSCs with distinct functional properties. To better understand the molecular mechanisms underlying the developmental switch, we have conducted deep sequencing of the 3D genome, epigenome, and transcriptome of fetal and adult HSCs in mouse. We find that chromosomal compartments and topologically associating domains (TADs) are largely conserved between fetal and adult HSCs. However, there is a global trend of increased compartmentalization and TAD boundary strength in adult HSCs. In contrast, intra-TAD chromatin interactions are much more dynamic and widespread, involving over a thousand gene promoters and distal enhancers. These developmental-stage-specific enhancer-promoter interactions are mediated by different sets of transcription factors, such as TCF3 and MAFB in fetal HSCs, versus NR4A1 and GATA3 in adult HSCs. Loss-of-function studies of TCF3 confirm the role of TCF3 in mediating condition-specific enhancer-promoter interactions and gene regulation in fetal HSCs.

Keywords: 3D genome; enhancer-promoter interaction; epigenomics; hematopoiesis; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism*
  • Animals
  • Enhancer Elements, Genetic / genetics
  • Female
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Male
  • Mice
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
  • Promoter Regions, Genetic / genetics


  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1