Bone Marrow Mesenchymal Stem Cells Carrying FANCD2 Mutation Differ from the Other Fanconi Anemia Complementation Groups in Terms of TGF-β1 Production

Stem Cell Rev Rep. 2018 Jun;14(3):425-437. doi: 10.1007/s12015-017-9794-5.


Transforming growth factor beta (TGF-β) secretion from cells in the bone marrow (BM) niche affects hematopoietic stem cell (HSC) fate and has a cardinal role in HSC quiescence. BM mesenchymal stem cells (BM-MSCs), a component of the BM niche, may produce abnormal levels of TGF-β in Fanconi anemia (FA) and may play a role in bone marrow failure. Here, we molecularly and cellularly characterized FA BM-MSCs by addressing their immunophenotype, proliferation- and differentiation- capacity, reactive oxygen species (ROS) production, senescence activity as well as expression and secretion levels of TGF-β isoforms. In ten FA patients, mutations were detected in FANCA (n = 7), FANCG (n = 1) and FANCD2 (n = 2) genes. The immunophenotype, with the exception of CD29, and differentiation capacity of FA BM-MSCs were similar to healthy donors. FA BM-MSCs showed decreased proliferation, increased ROS level and an arrest in G2 following DEB treatment. β-galactosidase staining indicated elevated senescence of FANCD2-deficient cells. FA BM-MSCs displayed TGF-β1 mRNA levels similar to donor BM-MSCs, and was not affected by DEB treatment. However, secretion of TGF-β was absent in FA-D2 BM-MSCs. Absence of TGF-β secretion may be related to early onset of senescence of the FANCD2-deficient BM-MSCs. The proliferative response of FA-D2 BM-MSCs to rTGF-β1 was not different from FANCA-deficient and donor cells and raises the possibility that rTGF-β1 may reverse the senescence of the FANCD2-deficient BM-MSCs which needs to be investigated further.

Keywords: Bone marrow; FANCD2; Fanconi anemia; Mesenchymal stem cells; TGF-BETA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cells, Cultured
  • DNA Mutational Analysis
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism*
  • Fanconi Anemia Complementation Group D2 Protein / genetics*
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • Fanconi Anemia Complementation Group G Protein / genetics
  • Fanconi Anemia Complementation Group G Protein / metabolism
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Mutation / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Transforming Growth Factor beta1 / metabolism*


  • FANCG protein, human
  • Fanconi Anemia Complementation Group D2 Protein
  • Fanconi Anemia Complementation Group G Protein
  • Transforming Growth Factor beta1