Format

Send to

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

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

Author information

1
Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
2
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Sol Sherry Thrombosis Research Center, Temple University Medical School, Philadelphia, PA 19140, USA.
4
Department of Computer Science, University of Missouri-Columbia, Columbia, MO 65211, USA.
5
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
6
Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: tank1@email.chop.edu.

Abstract

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

PMID:
31851943
DOI:
10.1016/j.celrep.2019.11.065
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center