Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells

Nat Immunol. 2011 Feb;12(2):129-36. doi: 10.1038/ni.1978. Epub 2010 Dec 26.


The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resulted in the downregulation of many transcripts required for HSC maintenance. Genome-wide profiling by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex-binding sites at highly conserved regions in the promoters of genes involved in HSC maintenance. Our results identify a central role for Ldb1 in regulating the transcriptional program responsible for the maintenance of HSCs.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Adult Stem Cells / cytology
  • Adult Stem Cells / immunology
  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / transplantation
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / immunology
  • Embryonic Stem Cells / metabolism*
  • Embryonic Stem Cells / transplantation
  • Female
  • Fetal Development* / genetics
  • Fetal Development* / immunology
  • Gene Expression Regulation, Developmental / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism*
  • High-Throughput Nucleotide Sequencing
  • LIM Domain Proteins
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Pregnancy
  • Protein Binding
  • Regulatory Elements, Transcriptional / genetics
  • Regulatory Elements, Transcriptional / immunology
  • Transcriptional Activation / genetics
  • Transcriptional Activation / immunology


  • DNA-Binding Proteins
  • LIM Domain Proteins
  • Ldb1 protein, mouse

Associated data

  • GEO/GSE26031