Periodic Reporting for period 2 - ESPACE (Human Cell Atlas of the Pancreas)
Période du rapport: 2021-07-01 au 2022-06-30
The human pancreas is a physiologically unique organ involved in the secretion of several hormones. The organ regulates blood sugar levels as well as the secretion of enzymes for the digestive tract. Several human diseases are associated with the pancreas: Pancreatic adenocarcinoma (PDAC) is one of the most aggressive cancers in humans and pancreatitis is a common potentially life-threatening disorder related to adverse lifestyle conditions. A very common chronical disease affecting the pancreas is type 2 diabetes (T2D), a metabolic disorder that is characterized by high blood sugar levels due to the lack of insulin produced in the pancreas endocrine islets. Despite its high physiological importance, the high autolytic activity makes the pancreas a very challenging tissue to study. Furthermore, diabetes plays an important role as risk factor in COVID-19 disease severity or possibly as long-COVID-19 symptom. We have generated molecular profiles on cellular level, including transcriptome and epigenomics data from more than 1 million single nuclei jointly together with tissue proteomics allowing to address fundamental questions of cell state and phenotype in healthy adults and during foetal development. Thus, we intend to present a first version of an open single-cell repository of the pancreas that sufficiently describes all cell types in healthy tissue, in T2D and changes during aging. Probably, most interesting are the many different micropathological lesions studied in healthy human pancreata of the fifth decade. Towards publication of the data, we implemented a cloud-based analysis platform which will serve as data portal of ESPACE.
In particular, the ESPACE Human Cell Atlas project provides multiomic characterization of pancreas organ including proteomics and genomics. We conducted separate sequencing of single-cells or -nuclei and spatial proteomics technologies, including 16 different individuals and 4 different locations in the respective donated pancreatic organs. Due to quality issues, we explicitly decided to run single nuclei RNA and epigenetics sequencing separately to achieve most precise outputs from the different experimental branches.
Due to the pandemic and corresponding delays, the consortium was also affected in exchange and communication within. This will further delay the first comprehensive cell atlas of the pancreas, although all the projected data is stored, we worked on cloud-based analysis and dissemination output (joined publications).
On the other hand, single-nuclei sequencing pancreas protocols really helped to study post-mortem respiratory, brain and lung COVID-19 samples. This should be considered as a wider societal and scientifical impact in the pandemic.
Our single-nuclei RNA sequencing pancreas protocols greatly helped to study post-mortem respiratory, brain and lung COVID-19 samples. Using this expertise, we were able to support the efforts of the scientific community in understanding the molecular mechanisms activated during/after the SARS-CoV-2 infection.