Gene Regulation, Stems Cells and Cancer

Hematopoietic Differentiation and Stem Cell Biology

Group Structure

Thomas Graf (ICREA Research Professor)
Chris van Oevelen
Jose Luis Sardina (CRG), Tian Tian (BLUEPRINT)
Luisa de Andres (CRG), Francesca Rapino (“la Caixa”), Bruno Di Stefano (“la Caixa”), Andreas Lackner (Plan Nacional)
Clara Berenguer (Plan Nacional), Laura Batlle (CRG, GRSC programme)


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).