Rickard Sandberg, Ludwig Institute for Cancer Research, Stockholm
Rickard
Sandberg
Genomics
Bio

I am a biologist interested in understanding the control of gene expression during development and in disease. My expertise is in developing and applying genomic technologies that can allow us to study gene expression at greater resolution (e.g. single-cell RNA-seq) and the computational methods needed to infer gene regulatory mechanisms.

My research is focused on developing methods that enable highly detailed analyses of the active portions of the genome in individual cells, in contrast to most methods that only measure the average behaviors across thousands of cells. Single-cell analyses are particularly relevant to cancer because tumor tissue is heterogeneous and often consists of several types of cells with different (complementing) abilities. We are very interested in determining how cells within a tumor differ from each other, and how the cellular compositions relate to prognosis and treatments. These analyses could pinpoint whether there are rare cells that survive treatments to later give rise to secondary tumors.

My lab has also used the single-cell methodology to study individual cells that break off from a tumor and enter the circulation. These circulating tumor cells are directly related to the spread of tumors, but they often exist in too few numbers to be studied with conventional methods. We have demonstrated that our methods can give molecular insights into these cells' unique abilities, with the aim of using this information to develop novel approaches for treatment.

Education
PhD, Microbiology and Tumor biology center, Karolinska Institute, 2004

Msc, Biomedicine, Karolinska Institute, 2000


Achievements

EMBO Young Investigator Award, 2012

Sven and Ebba-Christina Hagbergs Prize, 2012

Read More

Rickard Sandberg lab

My group is developing and applying single-cell transcriptomics to characterize cellular heterogeneity in cancer tissues and inside stem and progenitor cell compartments to map out the regulatory network that specifies cell identities and stem cell abilities. We also are analyzing the single-cell resolution gene expression data to unravel novel aspects of gene expression and regulation that are rapidly lost when analyzing average gene expressions across cell populations.

Rickard Sandberg, Ludwig Institute for Cancer Research, Stockholm
Rickard
Sandberg
Genomics
Bio

I am a biologist interested in understanding the control of gene expression during development and in disease. My expertise is in developing and applying genomic technologies that can allow us to study gene expression at greater resolution (e.g. single-cell RNA-seq) and the computational methods needed to infer gene regulatory mechanisms.

My research is focused on developing methods that enable highly detailed analyses of the active portions of the genome in individual cells, in contrast to most methods that only measure the average behaviors across thousands of cells. Single-cell analyses are particularly relevant to cancer because tumor tissue is heterogeneous and often consists of several types of cells with different (complementing) abilities. We are very interested in determining how cells within a tumor differ from each other, and how the cellular compositions relate to prognosis and treatments. These analyses could pinpoint whether there are rare cells that survive treatments to later give rise to secondary tumors.

My lab has also used the single-cell methodology to study individual cells that break off from a tumor and enter the circulation. These circulating tumor cells are directly related to the spread of tumors, but they often exist in too few numbers to be studied with conventional methods. We have demonstrated that our methods can give molecular insights into these cells' unique abilities, with the aim of using this information to develop novel approaches for treatment.

Education
PhD, Microbiology and Tumor biology center, Karolinska Institute, 2004

Msc, Biomedicine, Karolinska Institute, 2000


Achievements

EMBO Young Investigator Award, 2012

Sven and Ebba-Christina Hagbergs Prize, 2012

Read More

TEAM

Ilgar
Abdullayev
Bio

PhD student

Daniel
Edsgärd
Bio

Postdoctoral Fellow

Mtakai
Ngara
Bio

PhD student

Björn
Reinius
Bio

Postdoctoral Fellow

Åsa
Segerstolpe
Bio

Postdoctoral Fellow

Gösta
Winberg
Bio

Lab manager

Qiaolin
Deng
Bio

Postdoctoral Fellow

Omid
Faridani
Bio

Postdoctoral Fellow

Daniel
Ramsköld
Bio

PhD student

Sven
Sagasser
Bio

Postdoctoral Fellow

Helena
Storvall
Bio

PhD student

Chika
Yokota
Bio

Research Associate

RESEARCH AREAS

Using single-cell transcriptomics to investigate gene regulation, cellular heterogeneity
and the specification of cell identities

We are studying gene expression and regulation using a combination of genomic technologies. In particular, we are developing and applying single-cell transcriptomics to better understand how cellular identities are specified at the molecular level during differentiation, in pluripotency and to enable studies of the cellular heterogeneity in tumors. Single-cell analyses of cancer tissues promise new approaches for simultaneous investigation of cell types, heterogeneity and clonality through the combined analyses of gene expression patterns and mutations. Additionally, we believe that analyses of single-cell level gene expression will unravel general aspects of transcription processes and general rules for the composition of transcriptomes.

Click the links below to learn more.

Developing methods for single-cell transcriptomics

Recent developments in single-cell RNA-Seq have demonstrated that biologically meaningful transcriptome information can be reliably captured from individual cells. We worked with Illumina (Gary Schroth and colleagues) on Smart-Seq, a method that gives a very detailed representation of single-cell transcriptomes, and we demonstrated the extent of technical variability and biological significance in single-cell transcriptomics (Ramsköld et al. 2012). To expand the areas of applications further, we are working on improving Smart-Seq in terms of sensitivity, accuracy and lowering biases and costs. This will enable analyses of thousands of single cells in cancer-related projects.

 

Analyses of in vivo differentiation processes at single-cell resolution

We are studying mouse preimplantation development as a model system to study an in vivo differentiation process at single-cell resolution. Additionally, studying preimplantation development (the development of a fertilized egg into a blastocyst, ready to implant into the uterus) allows us to map gene regulatory events that specify how pluripotency is established and lost in vivo. To this end, we isolate embryos that are dissociated and subject to single-cell transcriptomics to characterize the gene expression programs inside individual cells of the developing embryo. In these studies, we are making use of mouse crosses to simultaneously gather allelic expression measurements from the individual cells.

 

Using single-cell transcriptomics to study tumor heterogeneity

We are eager to use the single-cell transcriptomics to study the cellular compositions inside solid tumors of diverse origin and to study their response to therapy and their relationship to metastatic tumors.

 

Using single-cell transcriptomics to study circulating tumor cells

Tumor cells are often found in the peripheral blood of cancer patients, and these circulating tumor cells are responsible for the origin of metastasis. In many cancers the number of circulating tumor cells in the bloodstream is low, and detailed molecular characterization of the them has not been feasible. Together with the Louise Laurents lab (University of California, San Diego), we demonstrated that it is possible to map detailed transcriptomes from circulating tumors cells. The transcriptome information was used to demonstrate that these cells were indeed tumor derived, thus validating the markers and procedure used to identify them. Additionally, the transcriptome could be queried for other alterations of the tumors cells that are likely associated with their migrating abilities. Altogether, single-cell transcriptomes is a very attractive method to gain molecular understanding of rare but clinically relevant cells.

 

Genome-wide analyses of gene expression and regulation

Our lab is also interested in integrating different genomic technologies and tools to study general mechanisms of transcriptional and post-transcriptional regulation. We recently performed the computational analysis of genome-wide data to demonstrate how a DNA-binding factor (CTCF) could affect alternative splicing through the promotion of RNA polymerase II pausing at variably included exons.

 

PUBLICATIONS

Deng Q, Ramsköld D, Reinius B, Sandberg R. Single-cell RNA-Seq reveals dynamic, random monoallelic gene expression in mammalian cells. Science 10 January 2014: Vol. 343 no. 6167 pp. 193-196.

Picelli S, Björklund ÅK, Faridani OR, Sagasser S, Winberg G, Sandberg R. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nature Methods 2013 Nov;10(11):1096-8.

Ramsköld D.*, Luo S.*, Wang Y-C, Li R., Deng Q., Daniels G.A., Khrebtukova I., Loring J.F., Laurent L.C., Schroth G.P., Sandberg R. (2012) Full-length mRNA-Seq from single cell levels of RNA and individual circulating tumor cells. Nature Biotechnology, 30, 777–782

*co-first authors

Wang ET*, Sandberg R*, Luo S., Khrebtukova I., Zhang Lu., Mayr C., Kingsmore S., Schroth G.P., and Burge C.B. (2008) Alternative Isoform Regulation in Human Tissue Transcriptomes. Nature Nov 27, 456, 470-476.

*co-first authors

Sandberg R.*, Neilson J.*, Sarma A, Sharp P. A., Burge C. B. (2008) Proliferating cells express mRNAs with shortened 3`UTRs and fewer microRNA target sites. Science. Vol 320. no. 5883, pp. 1643-1647

*co-first authors