Human Cell Atlas spatial pilot project towards assessing cellular heterogeneity and organization of an entire human organ

 

Project Purpose

Within the SPAN (Spatial pilot: PANcreas) we will develop workflows combining spatially resolved imaging of cells, single proteins and RNA molecules with droplet-based single cell sequencing and morphology in the human pancreas.

Project Summary

The human cell atlas aims at characterizing each and every single cell in the human organism to draw a comprehensive map of contextual normal human biology. While the community has seen dramatic developments in the field of single cell genomics technologies in recent years, a combination of high-throughput molecular sequencing of single cells with spatial analysis of the cellular microarchitecture in the context of an intact human organ is now badly needed to move our understanding of biology the next step forward. Here, we will develop workflows combining spatially resolved imaging of cells, single proteins and RNA molecules with droplet-based single cell sequencing and morphology in a human organ. In the proposed spatial pilot we chose to develop workflows for future human cell atlas projects along a pilot endeavor focusing on the human pancreas. This consortium integrates classical histomorphology, multi-epitope and mRNA in situ labelling with nuclei droplet sequencing of multiple regionally sampled probes of normal pancreas representing the whole normal organ structure to decipher biological heterogeneity and technical variation. Biological heterogeneity may appear between different individuals (pancreata) or intra-organic. Technical variation is assessed by replicates within and by comparison of pancreata specimen. Multimodal imaging and single nuclei analysis will generate probe overlap and sparsity, which requires data integration on cell centric levels. All data set, methods and workflows will be made publicly available according to HCA guidelines. The logistic setup of this pilot project will suggest dissemination and mediate strategies for further spatial HCA project designs.

 

Participants and Contacts

  • Roland Eils, Heidelberg University and DKFZ Heidelberg, Germany (Coordinator)
  • Garry Nolan, Stanford University, USA
  • Dana Pe'er, MSKCC New York, USA
  • Wilko Weichert, Technical University Munich, Germany
  • Xiaowei Zhuang, Harvard University, USA