Sandberg Lab

Ludwig Institute for Cancer Research & Department of Cell and Molecular Biology, Karolinska Institutet

welcome to sandberg lab

We are studying global aspects of gene regulation by combining genome-wide experimental and computational techniques to better understand stem cell characteristics and differentiation processes. We aim towards a better understanding of the molecular regulation of gene expression programs by the combined study of gene regulation acting on different levels (e.g. transcriptional and post-transcriptional) using next-generation sequencing techniques. In particular, we are interested in gene expression regulation of differentiation and cell fates during mouse early embryonic development, using single-cell RNA sequencing methods.

We are located at the Ludwig Institute for Cancer Research, Stockholm branch and the Department of Cell and Molecular Biology at Karolinska Institutet.

Funded Postdoc Position Available in Bioinformatics (see Positions)!


Paper on the genomic encoding of transcriptional burst kinetics out in Nature.

Transcription occurs in episodic bursts of varying frequencies and sizes. In this paper, we used single-cell RNA-sequencing with allelic resolution to infer the kinetics of transcription for genes expressed in tail fibroblasts and embryonic stem cells. We found multiple types of evidence supporting a transcriptome-wide role of enhancers in dictating burst frequencies, whereas core promoter elements affected burst size. read more here: Paper at Nature [Jan 2019]

Analysis of allelic expression in clonal somatic cells

It has been suggested in the literature that random monoallelic expression (RME) of autosomal genes is widespread and affect up to 10-15% of all genes. In this paper, we provide the first global single-cell analysis of allelic expression in clonal somatic cells and we found that clonal RME is scarce, whereas stochastic RME due to transcriptional bursting is widespread. Importantly, we performed these analyses in primary cells and on cells in vivo to reduce confounding results by chromosomal aberrations occurring in long-term cultured cells. The results are important, as the nature of RME will dictate its cellular consequences and possible phenotypic consequences. Read the paper in Nature Genetics. [Sep 2016]

Single-cell gene expression analysis of human pancreatic islets

Our single-cell RNA-seq resource article is just out in Cell Metabolism. In this work, that was carried out together with Astra Zeneca, we assign cell-type specific gene expression programs and identify sub-populations of exocrine and endocrine cells. The data is searchable here. [Sep 2016]

Transcriptional insights into human preimplantation developments and X-chromosome regulation

Single-cell gene expression analyses of human preimplantation embryos revealed new features of X-chromosome regulation. Our data revealed that dosage compensation initiates already pre-implantation and by biallelic dampening. This was a joint work with Fredrik Lanners lab at KI and was published in Cell. [May 2016]

Single-cell transcriptome analyses of innate lymphoid cells

In this work we sequenced the transcriptomes of index sorted ILCs to explore the heterogeneity of ILCs and to contrast protein and RNA expression in individual mammalian cells. This work is now out in Nature Immunology. This work was carried out by my lab in collaboration with Jenny Mjösberg's lab at KI. [Feb 2016]

Electrophysiological, transcriptomic and morphologic profiling of single neurons using Patch-seq

We have optimized a protocol to combine whole-cell patch clamp recordings with high-quality RNA-sequencing for individual neurons, which we refer to as Patch-seq. This approach should be very useful to unravel the molecular basis of cell type identity as well as the molecular basis of several electrophysiological properties across cell types and species. This work was a joint collaboration between our lab and the labs of Andreas Tolias, Kim Tolias and Matthias Bethge. [Dec 2015]

Appointed Professor in Molecular Genetics at KI

Rickard has been appointed Professor in Molecular Genetics at Karolinska Institutet, starting Nov 1st [Nov 2015]

Revisiting Random Monoallelic expression (review out in Nature Review Genetics)

In this review, we have revisited early observations on random monoallelic expression of autosomal genes (aRME) in the light of new insights from single-cell gene expression analysis with allelic resolution. We discuss recent genome-wide studies on bulk cell populations and single cells, the dynamic and clonal form of aRME and speculate on their cellular and phenotypic consequences. [Oct 2015]

Mapping of promoter-enhancer interactions with HiCap

We have developed a sequencing-based method for mapping interactions between promoters and distal genomic regions. Due to the four-cutter we obtain higher resolution than previous studies and are approaching single-enhancer resolution. Read the paper in Genome Biology. [Aug 2015]

ERC Consolidator Grant

The sandberg lab received a highly competitive Consolidator Grant from the European Research Council to continue our explorations of allelic expression patterns using single-cell RNA-sequencing. [May 2015]

Daniel Ramsköld's thesis awarded best PhD thesis at Karolinska Institutet 2014

Daniel Ramsköld recieved his Phd in June 2014 and was recently awarded the Dimitris N. Chorafas prize for his contributions to medical research. Read more...Congrats Daniel! [Oct 2014]

Transposase technology published

To allow for flexible and innovative moleular biology and deep sequencing, we have just realized our protocols for Tn5 production and use. It works even down to sub-picograms of input DNA! Read more. [Jul 2014]

Independent allelic transcription generates fluctuations in the single-cell transcriptome

Using the single-cell rna-sequencing methods developed within our lab, we have studied allelic transcription in individual cells form mouse preimplantation embryos. We discovered that many genes (~20%) had only RNA from one of the parental alleles at any given time of analyses, likely a consequence of pulsing allelic transcription. We desribe these allelic expression patterns in our study published in Science. [Jan 2014]

Single-cell transcriptomics 2.0

Our lab has developed an improved single-cell RNA-seq method (smart-seq2)! It more sensitive, automation-friendly, has lower bias, see our recent publication in Nature methods for details. For comprehensive details on smart-seq2 library preparations, please see our Nature Protocol. [Sep 2013]

A reference transcriptome and inferred proteome of the red spotted newt

Together with Andras Simon's lab we have generated a comprehensive reference transcriptome for the red spotted newt. Our study is now out in Experimental Cell Research, and the reference transcriptome, proteome and annotations are available here. [Mar 2013]

MULTo: comprehensive uniqueness files for NGS

Tired of generating uniqueness files for different read lengths. Download and use our uniqueness files that cover read lengths from 20-255 in one single file. This resource was recently published in PLoS ONE. [Jan 2013]

Single-cell RNA-Sequencing of circulating tumor cells using Smart-Seq

Our study describing Smart-Seq for analyses of gene expression in individual cells is now out in Nature Biotechnology. [publications] [Jul 2012]

Sequentially Acting Sox Transcription Factors in Neural Lineage Development

We have worked together with Jonas Muhrs lab on the genome-wide mapping of Sox transcription factors at different developmental stages in neural development. Interestingly, we found that factors pre-bind regions that will be first activated at subsequent developmental stage, often by another Sox factor. This study has now been published in Genes & Development. [Nov 2011]

CTCF promotes RNA pol II pausing and pre-mRNA splicing

We have been working together with Shalini Oberdoerffers lab on the effects of DNA-binding protein CTCF on pre-mRNA splicing. This work is now out in Nature (AOP, Oct 2nd) [Oct 2011]

Future Research Leader Grant (FFL4)

The sandberg lab received a long-term grant from the Swedish Foundation for Strategic Research so that our research areas will continue to expand during the coming years [Dec 2010]

Move to Ludwig Institute

We have moved the lab to Ludwig Institute for Cancer Research, Stockholm branch. New contact address is Nobels väg 3. [Jun 2010]

An Abundance of Ubiquitously Expressed Genes Revealed by RNA-Seq

Using RNA-sequencing data from human and mouse tissues we explored general features of tissue transcriptomes. This work was done in collaboration with Burge lab (MIT) and is now out in PLoS Comp Biol. [Dec 2009]

ERC Starting Grant

The sandberg lab received a highly competitive Starting Grant from the European Research Council, therefore the lab will be expanding over the next few years. [Sep 2009]

RNA-seq of human tissue transcriptomes

Alternative mRNA regulation across human tissues and cell lines was investigated by illumina/solexa mRNA sequencing. This was a collaboration with Burge lab (MIT) and Schroth and co-workers at Illumina, Hayward. This work is now out in Nature. [Oct 2008]

3'UTR shortening in proliferation cells paper published

The study on dynamical regulation of 3' untranslated regions is now published in Science (see publications). [Jun 2008]

Poster Award, Systems Biology Meeting at CSHL

The poster ("Widespread evasion of post-transcriptional regulation associated with proliferation." by Sandberg*, Neilson*, Sarma,Sharp and Burge) won the only Poster Price at the Systems Biology: Global Regulation of Gene Expression meeting in Cold Spring Harbor, NY, USA March 27-30, 2008. The poster presented the study of 3'UTR dynamics in activated immune cells and in proliferation. [Mar 2008]

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