The SFO supports three researchers at Karolinska Institutet
The SFO (Stem cells and Regenerative medicine) has decided to support three researchers at Karolinska Institutet. Read their project descriptions below
We will introduce molecular barcodes in stem/progenitor cells in mice using gene editing. We will simultaneously interrogate the identity of the barcodes and thus the cell lineage, and the transcriptome of the cells by spatial transcriptomics. We will furthermore perform single cell transcriptome and whole genome sequencing from human cells to make phylogenetic trees based on mutation patterns to establish the origin of new cells. The goal of the project is to develop generally applicable methodology for the analysis of cell lineages and transcriptome in regenerative medicine, and apply it for the analysis of adult neurogenesis in the healthy brain and after stroke.
Recent findings have shown that the hematopoietic stem cell (HSC) population is composed of functionally different lineage-biased HSCs. The mechanisms governing this HSC heterogeneity are insufficiently explored. Mutations in epigenetic regulators in HSCs of older healthy individuals predispose for hematologic disease, suggesting that epigenetic regulation is important for normal HSC lineage commitment. Thus, uncovering the epigenetic machinery responsible for HSC heterogeneity and fate determination is important for both normal blood cell development and for pre-malignant and malignant blood development. In this project we will investigate the epigenomic profiles of lineage-biased HSCs to map out the epigenetic landscape. Furthermore, the significance of epigenetic processes in determining HSC lineage bias will be explored in greater detail by investigating the role of histone deacetylases (HDACs) in this process.
Pediatric Acute Lymphoblastic Leukemia (ALL) arises from lymphocyte progenitors and is known to maintain a hierarchy of cell differentiation, making it a suitable model disease for studying cancer stem cells. Although cure rates for ALL are currently above 80%, the prognosis of patients with relapsed ALL is dismal, with an overall survival rate of only 30%. We are analyzing primary and relapsed ALL from the same patient, with the aim of determining the clonal structure of the leukemia and characterize the cancer stem cell population in the primary sample of patients which later relapse. To differentiate between genetic and epigenetic changes, we are using a novel method that allows us to obtain genotypic and transcriptomic data from the same single cell, allowing us to trace clonal expansions that are mainly driven by epigenetic factors as well as those driven by genetic alterations.