Gene Regulation, Stems Cells and Cancer

thomas-graf
Hematopoietic Differentiation and Stem Cell Biology

Group Structure

GROUP LEADER:
Thomas Graf (ICREA Research Professor)
STAFF SCIENTIST:
Chris van Oevelen
POSTDOCTORAL FELLOWS:
Jose Luis Sardina (CRG), Tian Tian (BLUEPRINT)
PhD STUDENTS:
Luisa de Andres (CRG), Francesca Rapino (“la Caixa”), Bruno Di Stefano (“la Caixa”), Andreas Lackner (Plan Nacional)
TECHNICIANS:
Clara Berenguer (Plan Nacional), Laura Batlle (CRG, GRSC programme)

Summary

The laboratory’s main interests are the mechanisms of transcription factor-induced transdifferentiation of hematopoietic cells. More specifically, we investigate the C/EBPa induced conversion of B cells into macrophages, which can be achieved within 2 to 3 days at nearly 100% efficiency. We have recently also discovered that a pulse of C/EBPa can poise B cells to rapid and highly efficient reprogramming into induced pluripotent stem (iPS) cells. We are investigating how this process occurs at the molecular level. Finally, a smaller part of the lab studies the function of genes required to establish and maintain the hematopietic stem cell phenotype.
Figure 3 Figure 1


Research Projects

  • How does C/EBPa induce the transdifferentiation of pre-B cells into macrophages?
  • C/EBPa poises B cells for rapid reprogramming into iPS cells

Figure 2 Figure 2


Selected Publications

  1. Di Stefano B, Sardina JL, van Oevelen C, Kallin EM, Collombet S, Kalin EM, Vicent GP, Lu J, Thieffry D, Beato M, Graf T.
    “C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells”
    Nature, doi: 10.1038/nature12885. Epub 2013 Dec 15.
  2. Rapino F, Robles EF, Richter-Larrea JA, Kallin EM, Martinez-Climent JA, Graf T.
    “C/EBPα induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity.”
    Cell Rep, 3(4):1153-63 (2013).
  3. Gekas C, Graf T.
    “CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age.”
    Blood, 121(22):4463-72 (2013).
  4. Barneda-Zahonero B, Román-González L, Collazo O, Rafati H, Islam AB, Bussmann LH, di Tullio A, De Andres L, Graf T, López-Bigas N, Mahmoudi T, Parra M.
    “HDAC7 is a repressor of myeloid genes whose downregulation is required for transdifferentiation of pre-B cells into macrophages.”
    PLoS Genet, 9(5):e1003503 (2013).
  5. Choudhury NR, de Lima Alves F, de Andrés-Aguayo L, Graf T, Cáceres JF, Rappsilber J, Michlewski G.
    “Tissue-specific control of brain-enriched miR-7 biogenesis.”
    Genes Dev, 27(1):24-38 (2013).
  6. van Oevelen C, Kallin EM, Graf T.
    “Transcription factor-induced enhancer modulations during cell fate conversions.”
    Curr Opin Genet Dev, 23(5):562-7 (2013).