Zooming in on Diabetes Journal Club April 8, 2021
Zooming in on Diabetes Thursday, April 8 at 09:00 am (PST)
Presenter: Anni Zhang, Graduate Student – PhD program, Johnson Lab, Life
Sciences Institute, University of British Columbia (Vancouver)
Title of Paper: Single-Nucleus and In Situ RNA-Sequencing Reveal Cell
Topographies in the Human Pancreas
Abstract: Background & aims: Molecular evidence of cellular heterogeneity in the
human exocrine pancreas has not been yet established because of the local
concentration and cascade of hydrolytic enzymes that can rapidly degrade cells
and RNA upon pancreatic resection. We sought to better understand the
heterogeneity and cellular composition of the pancreas in neonates and adults in
healthy and diseased conditions using single-cell sequencing approaches.
Methods: We innovated single-nucleus RNA-sequencing protocols and profiled
more than 120,000 cells from pancreata of adult and neonatal human donors. We
validated the single-nucleus findings using RNA fluorescence in situ hybridization,
in situ sequencing, and computational approaches. Results: We created the first
comprehensive atlas of human pancreas cells including epithelial and nonepithelial
constituents, and uncovered 3 distinct acinar cell types, with possible implications
for homeostatic and inflammatory processes of the pancreas. The comparison
with neonatal single-nucleus sequencing data showed a different cellular
composition of the endocrine tissue, highlighting the tissue dynamics occurring
during development. By applying spatial cartography, involving cell proximity
mapping through in situ sequencing, we found evidence of specific cell type
neighborhoods, dynamic topographies in the endocrine and exocrine pancreas,
and principles of morphologic organization of the organ. Furthermore, similar
analyses in chronic pancreatitis biopsy samples showed the presence of acinar-
REG+ cells, a reciprocal association between macrophages and activated stellate
cells, and a new potential role of tuft cells in this disease. Conclusions: Our human
pancreas cell atlas can be interrogated to understand pancreatic cell biology and
provides a crucial reference set for comparisons with diseased tissue samples to
map the cellular foundations of pancreatic diseases.
URL link to publication source: https://pubmed.ncbi.nlm.nih.gov/33212097
“Zooming in on Diabetes” is a virtual journal club and was launched in March 2020.
It is a joint initiative across the University of British Columbia campuses including the Life Sciences Centre and the BC Children’s Hospital.
This Journal Club is designed for trainees to develop skills in critical evaluation of recent articles in the scientific literature related to diabetes research.
The intended audience are academic research trainees and faculty involved in diabetes research in British Columbia, Canada.
The journal club is held on Tuesdays and Thursdays via ZOOM.