Stem Cell Biology and Regenerative Medicine
Hematopoietic Development from Human Pluripotent Stem Cells
The main focus of research in my lab is to significantly advance the clinical use of stem cells through development of novel sources of hematopoietic stem cells and mature blood cells for transplantation, transfusion and cancer immunotherapy. We use integrative approaches, including genomics, proteomics and bioinformatics, to achieve the outlined goals and to understand important cellular, and molecular events leading to blood cell development and diversification. We already developed a very efficient system for hematopoietic and endothelial differentiation of human pluripotent stem cells (PSCs), and directed differentiation of PSCs toward red blood cells, dendritic cells, macrophages, osteoclasts, and granulocytes. In addition, we defined the major cellular pathways leading to formation of blood cells and identified several novel hematoendothelial, hematopoietic and mesenchymal progenitors. Through comparative analysis of transcriptome and engraftment properties of these novel progenitors and fetal primitive blood cells as well as employing loss-of- and gain-on-function and lienage-tracing experiments, we expect to gain fundamental insights into molecular mechanisms leading to blood cell development. We also employ MHC defined nonhuman primate model to facilitate the translation of pluripotent stem cell-based blood therapies to the clinic.
Molecular Determinants of Hemogenic Endothelium
Hemogenic endothelium (HE) has been recognized as a source of HSCs in the embryo. Recently we identified the exact phenotype of HE in human pluripotent stem cell cultures. Currently, we focus on studies of molecular network regulating the formation of HE and endothelial-hematopoiteic transition using human pluripotent stem cell models.
Reprogramming of non-hematopoietic somatic cells into the blood cells.
The reprogramming studies provided strong evidence that cellular identities are defined by gene regulatory networks controlled by few master regulatory factors. We are looking to identify transcriptional factors capable to induce blood and HSC program in non-hematopoietic somatic cells. Knowledge gained from these studies will be used to define gene network controlling hematopoietic fate.
Reprograming leukemia to study leukemia stem cells function
A definitive cure for leukemia will require identifying novel therapeutic targets to eradicate leukemia stem cells (LSCs). However, the rarity of LSCs within the pool of malignant cells remains a major limiting factor for their study in humans. We showed that primitive hematopoietic cells with typical LSC features can be generated de novo from reprogrammed primary chronic myeloid leukemia (CML) cells. We are using leukemia iPSC model to identify novel factors implicated in LSC survival.
Development of vasculogenic cells from human pluripotent stem cells
Recently, we discovered mesenchymoangioblast as a novel multipotential precursor for endothelial, mesenchymal stem cells, pericytes and smooth muscle cells, as well as other types of endothelial progenitors. We study the functional role of these progenitors in vasculogenesis and tissue regeneration.
Igor Slukvin, MD, PhD
Department of Pathology and Laboratory Medicine
University of Wisconsin