Johan Holmberg's Group

The vertebrate nervous system consists of a multitude of different cell types each with a unique identity and function. How this cellular diversity is generated during development and how the established neuronal identity is subsequently maintained are the main research interests of the group.

  1. How are alternative lineages shut down during neurogenesis and what are the consequences if this silencing fails? The generation of neurons from a pool of multipotent stem cells depends on instructive factors that activate the necessary gene programs to acquire neuronal identity. In parallel, neurogenesis is characterized by the progressive silencing of non-neuronal properties. Our aim is to understand the mechanisms governing repression of alternative lineages during neurogenesis and the functional consequences of errors in this process.
  2. How is a stable differentiated cellular state maintained? Maintenance of a differentiated phenotype is crucial for intact tissue function. Despite the recent surge of studies on how a handful of factors can induce pluripotency in somatic cells, the understanding of how a differentiated state is maintained remains rudimentary. Our aim is to explore mature neurons are protected from cell cycle reentry and loss of identity.
  3. Is glioma malignancy determined by the presence of ? The identification of tumor residing cells endowed with stem cell properties implies that a restricted cancer stem cell (CSC) population is capable to initiate and sustain tumor growth. Despite intense research efforts, the question whether tumor growth is driven by CSCs or whether the cell of origin is a somatic stem cell remains unresolved. We are focusing on the role played by the embryonic stem cell associated transcription factors in bestowing stem cell properties to glioma cells.

Group Member

Johan Holmberg Senior researcher
Vilma Rraklli PhD student
Yao Shi Postdoc
Erik Södersten Postdoc
Isabelle Westerlund PhD student

Selected Publications

Elevated levels of ZAC1 disrupt neurogenesis and promote rapid in vivo reprogramming.
Rraklli V, Södersten E, Nyman U, Hagey D, Holmberg J
Stem Cell Res 2016 Jan;16(1):1-9

PKCζ regulates Notch receptor routing and activity in a Notch signaling-dependent manner.
Sjöqvist M, Antfolk D, Ferraris S, Rraklli V, Haga C, Antila C, et al
Cell Res. 2014 Apr;24(4):433-50

CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression.
Egan C, Nyman U, Skotte J, Streubel G, Turner S, O'Connell D, et al
Dev. Cell 2013 Aug;26(3):223-36

Maintaining differentiated cellular identity.
Holmberg J, Perlmann T
Nat. Rev. Genet. 2012 May;13(6):429-39

EphB receptors coordinate migration and proliferation in the intestinal stem cell niche.
Holmberg J, Genander M, Halford M, Annerén C, Sondell M, Chumley M, et al
Cell 2006 Jun;125(6):1151-63

Developmental BiologyStem Cell Biology