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A single-cell genomics approach integrating gene expression, lineage, and physical interactions

Objective

From populations of unicellular organisms to complex tissues, cell-to-cell variability in phenotypic traits seems to be universal. To study this heterogeneity and its biological consequences, researchers have used advanced microscopy-based approaches that provide exquisite spatial and temporal resolution, but these methods are typically limited to measuring a few properties in parallel. On the other hand, next generation sequencing technologies allow for massively parallel genome-wide approaches but have, until recently, relied on studying population averages obtained from pooling thousands to millions of cells, precluding genome-wide analysis of cell-to-cell variability. Very excitingly, in the last few years there has been a revolution in single-cell sequencing technologies allowing genome-wide quantification of mRNA and genomic DNA in thousands of individual cells leading to the convergence of genomics and single-cell biology. However, during this convergence the spatial and temporal information, easily accessed by microscopy-based approaches, is often lost in a single-cell sequencing experiment. The overarching goal of this proposal is to develop single-cell sequencing technology that retains important aspects of the spatial-temporal information. In particular I will focus on integrating single-cell transcriptome and epigenome measurements with the physical cell-to-cell interaction network (spatial information) and lineage information (temporal information). These tools will be utilized to (i) explore the division symmetry of intestinal stem cells in vivo; (ii) to reconstruct the cell lineage history during zebrafish regeneration; and (iii) to determine lineage relations and the physical cell-to-cell interaction network of progenitor cells in the murine bone marrow.

Host institution

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Net EU contribution
€ 2 000 000,00
Address
Kloveniersburgwal 29 Het Trippenhuis
1011 JV Amsterdam
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Other
Non-EU contribution
€ 0,00

Beneficiaries (2)

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Netherlands
Net EU contribution
€ 2 000 000,00
Address
Kloveniersburgwal 29 Het Trippenhuis
1011 JV Amsterdam

See on map

Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Other
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands
Net EU contribution
€ 500 000,00
Address
Heidelberglaan 100
3584 CX Utrecht

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Region
West-Nederland Utrecht Utrecht
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00