Human Cell Atlas of the Pancreas

Informazioni relative al progetto

ESPACE

ID dell’accordo di sovvenzione: 874710

DOI

10.3030/874710

Progetto chiuso

Data della firma CE 13 Dicembre 2019

Data di avvio 1 Gennaio 2020

Data di completamento 30 Giugno 2022

Finanziato da

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Costo totale

€ 4 962 494,75

Contributo UE

€ 4 962 494,75

Coordinato da

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany

CORDIS fornisce collegamenti ai risultati finali pubblici e alle pubblicazioni dei progetti ORIZZONTE.

I link ai risultati e alle pubblicazioni dei progetti del 7° PQ, così come i link ad alcuni tipi di risultati specifici come dataset e software, sono recuperati dinamicamente da .OpenAIRE .

Risultati finali

Websites, patent fillings, videos etc. (1)

Integrative analysis based on merged data repository

We will perform an integrative analysis based on merged data repository combining all datasets obtained

Other (5)

Pipeline ESPACE (Human Cell Atlas of the Pancreas)

The ESPACE pipeline will be provided to HCA community

Integrative analysis of D3.1 and D.3.2 data, compared to those generated from healthy pancreata in WP2

Data from isolated islets from the adultD and T2D groups will be compared to each other and compared to the healthy pancreas adult group

sNucRNA Seq data from isolated islets from the adultD and T2D groups

sNucRNA Seq will be performed for ten ideally five male five female isolated islets from the T2D group and four ideally two male two female isolated islets from the agesex matched adultD group

Project Website

The project website will form a central platform to showcase all aspects of the project including information on the consortium and its members the project objectives and workplan upcoming events and project publications Social media links will facilitate the widespread dissemination of information

Epigenomic map analysis of purified alpha, beta and delta cell populations from the adultD and T2D groups

We will perform epigenomic profiling of isolated islets in bulk from adultD and T2D samples DNA methylation and histone modifications procured in WP1

Documents, reports (16)

Dissemination toolkit

The dissemination toolkit will be provided to all partners and will include a professional corporate identity including a project logo and styleguide dissemination and marketing materials such as project postcards or lanyards and templates for presentations reports meeting and internal documents

Protocol for IHC in freshly frozen and FFPE pancreas samples

TUM will provide the protocol for immunohistochemistry in freshly frozen and FFPE pancreas samples

Highly multiplexed imaging of 25 TMA using panels from D4.2 and D4.3

We will perform highly multiplexed imaging of 25 TMA with about 25 TMA core samples per array summing up to a total of over 600 samples

First Industry working group meeting

Report on the first meeting of the IT industry working group as established by STZ

Validated antibody panel for cell identity candidates

We will generate a novel antibody panel containing markers for candidate proteins with variable expression in subtypes of the known pancreas cells and validate it for usage in freshly frozen and FFPE pancreas samplesWe will use the HPA resource to create novel validated antibody panels for subsequent high parametric analysis of protein expression in the pancreas using the CODEX technology The antibody panel will be generated and validated for usage in freshly frozen and FFPE pancreas samples and contain the following a markers for known cell types in pancreas D44 b candidate proteins with variable expression in subtypes of the known pancreas cells D45 c a proliferation marker and d markers for cellular organelles plasma membrane Golgi apparatus mitochondria nucleus to allow for cell segmentation and highdefinition phenotypic analysis

Provision of Infrastructure

Infrastructure for data storage as well as data and cloud computing will be provided

Validated antibody panel for known cell types and proliferation markers

We will generate a novel antibody panel containing markers for known cell types in pancreas, and validate it for usage in freshly frozen and FFPE pancreas samples

Assessment of tissue morphology

TUM will control the pancreatic tissue for any impairment of the pancreas architecture and cellular composition inflammatory or neoplastic change

Social media report

The social media report will summarize social media support centrally provided to the consortium as well as social media presence of the ESPACE project

Management SOPs

All relevant project management rules and regulations the final set of contractual documents project tasks and deliverables as well as an overview of all project internal workflows will be communicated to each partner and summarised in a booklet that will handed out at the kickoff meeting

Dockerised Pipelines

All single cell analysis pipelines will be developed following the HCA requirements ansd according to policies All pipelines will be provided via dockerized versions and being included into standardized analysis frameworks

Spatial analysis of cell identity candidate gene expression, cell types and cell type distribution

We will identify and analyse the cell types in the pancreas and their heterogeneity in terms of cell identity candidate gene expression combining image processing alignment deconvolution cell segmentation and quantification of all the markers included in the CODEX staining Based on a mixture of the tools of network theory and machine learning the spatial organization of both local and higher order cellular communities will be analysed

Standardisation of workflows

The team from TUM will distribute their standardised protocols and workflows to the people at LUMC and OSR who will be responsible for tissue sampling there

Report on annual project meetings

This deliverable will document annual project meetings including agenda participants decisions taken and initiated follow up activities

Training and workshop

In year 1 STZ will organise a workshop for the associated partners of ESPACE and further SMEs and companies that share the same interest in using the Human Cell Atlas of the Pancreas as reference map This workshop will present biological data the progress and the goals of the Human Cell Atlas of the Pancreas methodological improvements and efforts in the T2D part of the study A second workshop will be geared towards the health IT industries including European SMEs and global IT players and implemented in year 2 of the project

Second industry working group meeting

Report on the second meeting of the IT industry working group as established by STZ

Demonstrators, pilots, prototypes (6)

scRNA Seq from rare cell types from healthy pancreata from the adult group

scRNA Seq from rare cell types from healthy pancreata from the adult group will be performed on an Illumina NovaSeq6000 sequencing system Libraries will be multiplexed and sequenced to an average depth of 50100000 reads per cell

scATAC Seq from healthy pancreata from adult and foetal groups

Multiregional scATAC Seq of ten ideally five male five female pancreas samples from healthy adult individuals and of eight ideally two of each two gestation weeks between week 1220 foetal pancreas samples from gestation week 12 to 20

sNucRNA Seq from healthy pancreata from adult and foetal groups

sNucRNA Seq from healthy pancreata of ten ideally five male five female pancreas samples from adult individuals and of eight ideally two of each two gestation weeks between week 1220 foetal pancreas samples from gestation week 12 to 20

Pipelines in OTP

All single cell analysis pipelines will be included into our data processing framework One Touch Pipeline OTP

Protocol for the isolation of rare pancreas cell types using GateID for training

Protocol for the isolation of rare pancreas cell types using GateID for trainingidentification of physical properties of rare cell types in the cell sorter which are then isolated for highthroughput transcriptome profiling

Knowledge sharing with/training of partner teams in LUMC and OSR

TUM will share their knowledge with their partner teams in LUMC and OSR and provide necessary training to ensure standardised tissue sampling

Open Research Data Pilot (1)

Data Management Plan

The DMP will describe the data management life cycle for the data to be collected processed andor generated by ESPACE and will include information on the handling of research data during after the end of the project what data will be collected processed andor generated which methodology standards will be applied whether data will be sharedmade open access and how data will be curated preserved including after the end of the projectAny isses related to the protection of personal data will be dealt with in the respective ethics requirement POPD D71

Pubblicazioni

Peer reviewed articles (7)

Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19

Autori: Saskia Trump, Soeren Lukassen, Markus S. Anker, Robert Lorenz Chua, Johannes Liebig, Loreen Thürmann, Victor Max Corman, Marco Binder, Jennifer Loske, Christina Klasa, Teresa Krieger, Bianca P. Hennig, Marey Messingschlager, Fabian Pott, Julia Kazmierski, Sven Twardziok, Jan Philipp Albrecht, Jürgen Eils, Sara Hadzibegovic, Alessia Lena, Bettina Heidecker, Thore Bürgel, Jakob Steinfeldt, Christ
Pubblicato in: Nature Biotechnology, Numero 39/6, 2021, Pagina/e 705-716, ISSN 1087-0156
Editore: Nature Publishing Group
DOI: 10.1038/s41587-020-00796-1

SARS ‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells

Autori: Soeren Lukassen, Robert Lorenz Chua, Timo Trefzer, Nicolas C Kahn, Marc A Schneider, Thomas Muley, Hauke Winter, Michael Meister, Carmen Veith, Agnes W Boots, Bianca P Hennig, Michael Kreuter, Christian Conrad, Roland Eils
Pubblicato in: The EMBO Journal, Numero 39/10, 2020, ISSN 0261-4189
Editore: Nature Publishing Group
DOI: 10.15252/embj.20105114

Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D

Autori: Dana Avrahami, Yue J. Wang, Jonathan Schug, Eseye Feleke, Long Gao, Chengyang Liu, Ali Naji, Benjamin Glaser, Klaus H. Kaestner
Pubblicato in: Molecular Metabolism, Numero 42, 2020, Pagina/e 101057, ISSN 2212-8778
Editore: Elsevier GmbH
DOI: 10.1016/j.molmet.2020.101057

Single-Nucleus and In Situ RNA–Sequencing Reveal Cell Topographies in the Human Pancreas

Autori: Luca Tosti, Yan Hang, Olivia Debnath, Sebastian Tiesmeyer, Timo Trefzer, Katja Steiger, Foo Wei Ten, Sören Lukassen, Simone Ballke, Anja A. Kühl, Simone Spieckermann, Rita Bottino, Naveed Ishaque, Wilko Weichert, Seung K. Kim, Roland Eils, Christian Conrad
Pubblicato in: Gastroenterology, Numero 160/4, 2021, Pagina/e 1330-1344.e11, ISSN 0016-5085
Editore: W. B. Saunders Co., Ltd.
DOI: 10.1053/j.gastro.2020.11.010

Building a high-quality Human Cell Atlas

Autori: Orit Rozenblatt-Rosen, Jay W. Shin, Jennifer E. Rood, Anna Hupalowska, Aviv Regev, Holger Heyn
Pubblicato in: Nature Biotechnology, Numero 39/2, 2021, Pagina/e 149-153, ISSN 1087-0156
Editore: Nature Publishing Group
DOI: 10.1038/s41587-020-00812-4

COVID-19 severity correlates with airway epithelium–immune cell interactions identified by single-cell analysis

Autori: Robert Lorenz Chua, Soeren Lukassen, Saskia Trump, Bianca P. Hennig, Daniel Wendisch, Fabian Pott, Olivia Debnath, Loreen Thürmann, Florian Kurth, Maria Theresa Völker, Julia Kazmierski, Bernd Timmermann, Sven Twardziok, Stefan Schneider, Felix Machleidt, Holger Müller-Redetzky, Melanie Maier, Alexander Krannich, Sein Schmidt, Felix Balzer, Johannes Liebig, Jennifer Loske, Norbert Suttorp, Jür
Pubblicato in: Nature Biotechnology, Numero 38/8, 2020, Pagina/e 970-979, ISSN 1087-0156
Editore: Nature Publishing Group
DOI: 10.1038/s41587-020-0602-4

SSAM-lite: A Light-Weight Web App for Rapid Analysis of Spatially Resolved Transcriptomics Data

Autori: Tiesmeyer, Sebastian; Sahay, Shashwat; Müller-Bötticher, Niklas; Eils, Roland; Mackowiak, Sebastian D.; Ishaque, Naveed
Pubblicato in: Frontiers in Genetics, section: Computational Genomics, Numero 1, 2022, ISSN 1664-8021
Editore: Frontiers Media
DOI: 10.3389/fgene.2022.785877