Klump Lab

Generation of somatic stem and progenitor cells, in vitro

In all organisms, the constant replenishment of cells lost due to aging and tissue damage is guaranteed by somatic, tissue-resident stem cells. Because of their regenerative potential, these multipotent stem cells are prime targets for the treatment of a plethora of disorders. Our lab tries to understand how blood-forming stem cells (hematopoietic stem cells, HSCs) can be generated, in vitro, for future tailored cell- and gene therapy of patients

Development of hematopoietic stem- and progenitor cells from pluripotent stem cells, in vitro

Pluripotent stem cells, such as embryonic stem (ES-) or `reprogrammed´, induced pluripotent stem (iPS-) cells, are defined by their capability to develop towards cells of all three germ layers, ecto-, meso- and endoderm. In contrast to the mesodermal, multipotent HSCs, these cells can be stably propagated in culture and are relatively easily amenable to genetic intervention by homologous recombination. Hence, patient-specific `autologous´ iPS-cells are especially attractive for gene repair and subsequent directed differentiation towards HSCs, in vitro. Because  differentiation of pluripotent stem cells appears to autonomously recapitulate many aspects of the developing embryo, this model is also very useful for studying the control of cell fate decisions crucial for blood stem cell development, in vitro. We are studying in vitro hematopoiesis using pluripotent stem cells from mice and humans.

Funded by the Deutsche Forschungsgemeinschaft (DFG)

The homeodomain transcription factor HOXB4 and its impact on early hematopoietic progenitor development

To generate multipotent hematopoietic stem- and progenitor cells (HSPCs), in vitro, we take advantage of the homeodomain transcription factor HOXB4, which supports hematopoietic development of differentiating pluripotent stem cells (such as ES- or iPS-cells) when expressed ectopically and also mediates expansion of adult HSPCs, in vitro and in vivo. A deeper understanding of the molecular pathways influenced by HOXB4 during pluripotent stem cell differentation will help us to substantially improve protocols for the in vitro generation of HSPCs and, thus, allow us to omit ectopically expressed supportive transcription factors in future.

Deciphering the mechanism(s) of HOXB4 action during hematopoietic development and expansion of HSPCs

The molecular mechanisms how homeodomain transcription factors control self renewal and differentiation of hematopoietic stem and progenitor cells is still far from being clear. Although constitutive ectopic HOXB4 expression biases hematopoietic differentiation towards myelopoiesis and away from lymphopoiesis, it mediates a `benign´ HSC expansion without leading to leukemia, as observed with other HOX proteins, such as HOXB3 or HOXA10.

We have demonstrated that HOXB4 alters the sensitivity of many signaling pathways by changing the regulation of key genes involved in these processes. In turn, the activity of HOXB4 (i.e. transcriptional activation or repression of its target genes) appears to depend on the cell type itself and its context, the (micro)environment.
To gain a better understanding of the activities of this versatile transcription factor on HSC formation, self renewal and differentiation, we are identifying and studying its posttranslational modifications, protein interaction partners and their influence on target gene binding and expression.

Former lab-members (Master, M.D.- and Ph.D.-students)

  • Susanne Skibbe (Technician)
  • Mathias Manzel (Ph.D. student)
  • Anika Neureiter (until 2019)
  • Nadine Teichweyde (until 2017)
  • Hannah Döpper (until 2018)
  • Lara Kasperidus (until 2016)
  • Julia Ulbricht (until 2017)
  • Melanie Zuk (until 2015)
  • Martina Cremanns (until 2017)
  • Corinna Meyer (until 2014)
  • Jana Rückforth (until 2021)
  • Kristin Stolp (until 2014)

Peer Reviewed Publications:


Book Chapters: