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Bioinformatics Training and Education Program

june, 2021

17jun11:00 am12:00 pmA transcriptionally distinct subpopulation of healthy acinar cells exhibit features of pancreatic progenitors and pancreatic ductal adenocarcinoma

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Event Details

The intrinsic stochasticity of transcription leads to gene expression variation across cells in a clonal cell population. The expression variation can translate into phenotypic variation that can persist through several rounds of cell division. In the context of tumor initiation, such inter-cell variation within a normal tissue can cause a fraction of cells to assume “edge” transcriptional states that are primed for a transition toward malignancy. In such a framework, oncogenic mutations can interact with transcriptional priming to lead to malignant transformation.

We developed a two-stage test to find such transcriptional states in single-cell RNA-seq data from healthy pancreatic tissues and pancreatic ductal adenocarcinoma (PDAC) tumors. We found a subset of non-malignant pancreatic acinar cells, which we refer to as acinar edge (AE) cells, whose transcriptomes are highly diverged from a typical normal acinar cell and are much closer to a malignant state.  Gene expression changes in AE cells recapitulate known gene expression changes during PDAC initiation and pancreatitis, which provides a common transcriptomic basis between pancreatitis and PDAC. Most strikingly, the fraction of AE-like cells increased with age, with no underlying mutational basis. Coupled with our observation that gene expression changes in AE cells in mice mirrored those during Kras-G12D induction, our findings point to a strong contribution of AE cells, and non-genetic expression heterogeneity in general, to PDAC initiation.

WebEx Link:

https://cbiit.webex.com/cbiit/j.php?MTID=med94a210a2c7c80e76396498a7f7bf7b

 Meeting number: 172 241 0782

Meeting PW: jjM4nAT3e@4

Audio-only Call-in #: 1-650-479-3207 (Access code: 172 241 0782)

Time

(Thursday) 11:00 am - 12:00 pm

Location

Online

Organizer

Single Cell Users Group

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