Digitonin-facilitated delivery of imaging probes enables single-cell analysis of AKT signalling activities in suspension cells

The Analyst ◽  
2021 ◽  
Author(s):  
Siwen Wang ◽  
Nicole G. Perkins ◽  
Fei Ji ◽  
Rohit Chaudhuri ◽  
Zhili Guo ◽  
...  

Digitonin allows the delivery of cyclic peptide-based imaging probes into suspension cells. This method enables time-resolved single-cell profiling of AKT signalling activities.

2019 ◽  
Vol 1066 ◽  
pp. 13-20 ◽  
Author(s):  
Qi-Xuan Sun ◽  
Xing Wei ◽  
Shang-Qing Zhang ◽  
Ming-Li Chen ◽  
Ting Yang ◽  
...  

2020 ◽  
Vol 118 (3) ◽  
pp. 605a
Author(s):  
Bob Fregin ◽  
Fabian Czerwinski ◽  
Doreen Biedenweg ◽  
Salvatore Girardo ◽  
Stefan Groß ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karsten Bach ◽  
Sara Pensa ◽  
Marija Zarocsinceva ◽  
Katarzyna Kania ◽  
Julie Stockis ◽  
...  

AbstractIt is unclear how genetic aberrations impact the state of nascent tumour cells and their microenvironment. BRCA1 driven triple negative breast cancer (TNBC) has been shown to arise from luminal progenitors yet little is known about how BRCA1 loss-of-function (LOF) and concomitant mutations affect the luminal progenitor cell state. Here we demonstrate how time-resolved single-cell profiling of genetically engineered mouse models before tumour formation can address this challenge. We found that perturbing Brca1/p53 in luminal progenitors induces aberrant alveolar differentiation pre-malignancy accompanied by pro-tumourigenic changes in the immune compartment. Unlike alveolar differentiation during gestation, this process is cell autonomous and characterised by the dysregulation of transcription factors driving alveologenesis. Based on our data we propose a model where Brca1/p53 LOF inadvertently promotes a differentiation program hardwired in luminal progenitors, highlighting the deterministic role of the cell-of-origin and offering a potential explanation for the tissue specificity of BRCA1 tumours.


Author(s):  
Alexander Lind ◽  
Falastin Salami ◽  
Anne‐Marie Landtblom ◽  
Lars Palm ◽  
Åke Lernmark ◽  
...  

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