Quickscan Single Cell

22 September 2018
#Leukemia #Oncogenes #Sequencing #Progenitor cells #Single Cell Technology
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer that is characterized by the accumulation of 10 to 20 protein-altering mutations. To better understand in which order these mutations are acquired and in which progenitor cells this is initiated, the Jan Cools lab (VIB-KU Leuven Center for Cancer Biology) used single-cell sequencing of total bone marrow cells and CD34+CD38- multipotent progenitor cells for four T-cell ALL cases. Hierarchical clustering detected a dominant leukemia cluster at diagnosis, accompanied by a few smaller clusters harboring only a fraction of the mutations. Analysis of the order of mutations showed that loss of 9p21 (CDKN2A/B) and acquisition of fusion genes were rather early events, while NOTCH1 mutations were typically late events. Analysis of progenitor cells revealed that the first mutations can be acquired in either multipotent progenitors or in lymphoid progenitors. The team is currently continuing this study to determine how chemotherapy treatment has an effect on the clonal evolution in ALL.
De Bie et al., Leukemia 2018

#ZEB2 #Macrophages #Transcription Factor #Single Cell Technology
The team of Martin Guilliams, Charlotte Scott and Wouter T’Jonck (VIB-UGent Center for Inflammation Research) demonstrates that the transcription factor ZEB2 is crucial for the maintenance of the specific identities of tissue-resident macrophages. Using the 10X genomics platform (via the SCA), the researchers sequenced RNA from liver, lung, spleen, colon and brain macrophages from mice either expressing or lacking ZEB2. Analysis of this data in collaboration with the team of Yvan Saeys (VIB-UGent Center for Inflammation Research) led to multiple discoveries which would have been missed with bulk sequencing. Firstly, not all the macrophages in the conditional KO mice efficiently eliminated ZEB2, with a proportion of macrophages in each tissue (except brain) maintaining one copy of this gene. Discriminating between these different cells was crucial in understanding the function of ZEB2 in macrophages. Secondly, the team were able to redefine the genes which contribute to the tissue-specific identities of the different macrophages, without including genes arising from contaminating cells that were present in previous bulk sequencing data. Having redefined the identities of the different macrophages, it was clear that loss of ZEB2 dramatically altered these profiles in a tissue-specific way, rendering the macrophages unfit for their specific environment and leading to their loss from their tissue of residence.
Scott, T’Jonck et al., Immunity 2018

#Lung tumor #Atlas #Single Cell Technology
The lab of Diether Lambrechts (VIB-KU Leuven Center for Cancer Biology) together with the Bernard Thienpont Lab at KU Leuven and Els Wauters at UZ Leuven created a first complete atlas of all the cells in lung tumors. For this goal they studied almost 100,000 single cells individually and focused on the non-cancer cells in tumors (blood vessels, immune cells, fibrous cells). This led to the discovery that there are actually many more different cell types in lung tumors: 52 different types of cells were identified, versus the dozen cell types known to be present. Tumors are thus much more complex than hitherto appreciated. The research teams also analyzed cells from the lung outside the tumor and checked for each cell type how it is changed by the tumor. This revealed new ways in which tumors can be targeted. The demonstration that presence of some of these cells is associated with a worse survival of patients, further emphasizes the clinical importance of these findings.
Lambrechts et al., Nature Medicine 2018

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