Jonas Muhr's Group
We are examining how stem cells of the brain are regulated both during cortical development and to escape malignant transformation upon oncogenic insults.
How a single population of stem cells is regulated to generate different cell types at successive developmental time points, is a fundamental question that has important implications for developmental biology and regenerative medicine. To address this question our aim is to unveil molecular principles that give cortical radial glia cells (RGCs) the competence to generate an array of distinct projection neurons, in a precis temporal order. To reach this goal, our strategy is to combine genome wide and functional experiments in RGCs to identify and characterize cortical lineage determinants and their non-coding cis-regulatory modules.
Another focus of the lab is to understand how stem cells in the nervous system are prevented from malignant transformation upon oncogenic events. To address this question, we are examining how the activation of intrinsic defence mechanisms are regulated in brain stem cells. We are also interested in understanding how tumour suppressor programs can be activated in human glioma stem cells. By elucidating how tumour suppressor response programs can be activated in glioma stem cells, the ultimate goal of this project is to find more efficient therapeutic approaches to defuse these cells.
CYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and lineage commitment.
Hagey DW, Topcic D, Kee N, Reynaud F, Bergsland M, Perlmann T, Muhr J
Nat Commun 2020 06;11(1):2898
Sequentially acting SOX proteins orchestrate astrocyte- and oligodendrocyte-specific gene expression.
Klum S, Zaouter C, Alekseenko Z, Björklund ÅK, Hagey DW, Ericson J, Muhr J, Bergsland M
EMBO Rep 2018 11;19(11):
SOX2 regulates common and specific stem cell features in the CNS and endoderm derived organs.
Hagey DW, Klum S, Kurtsdotter I, Zaouter C, Topcic D, Andersson O, Bergsland M, Muhr J
PLoS Genet 2018 02;14(2):e1007224
SOX5/6/21 Prevent Oncogene-Driven Transformation of Brain Stem Cells.
Kurtsdotter I, Topcic D, Karlén A, Singla B, Hagey DW, Bergsland M, Siesjö P, Nistér M, Carlson JW, Lefebvre V, Persson O, Holmberg J, Muhr J
Cancer Res 2017 09;77(18):4985-4997
Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells.
Hagey DW, Zaouter C, Combeau G, Lendahl MA, Andersson O, Huss M, Muhr J
Genome Res 2016 07;26(7):908-17