Ioannis Kokkinopoulos

Biomedical Research Foundation | brfaa · Translational Research

In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now re...

Background: Embryonic stem (ES) cells are pluripotent cells with the ability to differentiate to any cell type of the resident organism. In recent years, significant advances have been made in using these cells to obtain large numbers of cardiomyocyte (CM)-like cells for scientific research and clinical application. A vast number of protocols have...

A surface marker that distinctly identifies cardiac progenitors (CPs) is essential for the robust isolation of these cells, circumventing the necessity of genetic modification. Here, we demonstrate that a Glycosylphosphatidylinositol-anchor containing neurotrophic factor receptor, Glial cell line-derived neurotrophic factor receptor alpha 2 (Gfra2)...

The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Cardiac progenitor cells (CPCs) that express the homeobox gene Nkx2-5 give rise to the endocardium. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5 ⁺ CPC...

The single curative measure for heart failure patients is a heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adult m...

The single curative measure for heart failure patients is total heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adu...

Background Heart failure is the major cause of death and morbidity in industrialized countries with an estimated 23 million people affected per year, representing 30% of all global deaths. Injury to the adult mammalian cardiac muscle, often leads to a heart attack due to irreversible loss of a large number of cardiomyocytes (CM) and other cardiac i...

Systemic lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). We examined whether patrolling HSPCs differ from bone-marrow HSPCs both in SLE and healthy individu...

Systemic Lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). By employing next-generation sequencing, we compared the gene transcription signatures of CD34+ HSP...

The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5+ cardiac progenitor cells (CPCs) that express the Sry-type HMG box gene Sox17 from embryonic day (E) 7.5...

Document S1. Supplemental Experimental Procedures, Figures S1–S7, and Schematic Diagram S1

Adventitial progenitor cells, including SCA-1⁺ and mesenchymal stem cells, are believed to be important in vascular remodeling. It has been shown that SCA-1⁺ progenitor cells are involved in neointimal hyperplasia of vein grafts, but little is known concerning their involvement in hyperlipidemia-induced atherosclerosis. We employed single-cell sequ...

Movie S1. Spontaneously Beating Cardiomyocytes Differentiated from GFRA2+/PDGFR-α+ Mouse Cardiac Progenitors after FACS Isolation, Related to Figure 2 After an additional 5 days culture in differentiation media, GFRA2+/PDGFR-α+ cells showed synchronized spontaneous contraction, suggesting that they can effectively differentiate into functional car...

Movie S2. Spontaneously Beating Cardiomyocytes Derived from FACS-Isolated hGFRA2+/hPDGFR-α+ Human Cardiac Progenitors, Related to Figure 4 FACS-isolated hGFRA2+/hPDGFR-α+ cells from human ESCs differentiated into spontaneously beating cardiomyocytes.

Mammalian peripheral retinal pigmented epithelium (RPE) cells proliferate throughout life, while central cells are senescent. It is thought that some peripheral cells migrate centrally to correct age-related central RPE loss. We ask whether this proliferative capacity is intrinsic to such cells and whether cells located centrally produce diffusible...

The mammalian central neural retina (CNR) lacks the capability to regenerate, a phenomenon retained by lower vertebrates. However, retinal stem cells have been isolated from the ciliary epithelium of the mammalian retina. Chx10 is a paired-like homeobox transcription factor gene expressed in the presumptive neural retina of the invaginating optic v...

Retinal stem cells have been isolated from the ciliary epithelium (CE) of the mammalian retina. However, the central neural retina (CNR) lacks the capability to regenerate, a phenomenon retained by lower vertebrates. Mutations in the Chx10 homeobox gene cause reduced proliferation of retinal progenitor cells during development, leading to microphth...

The innate immune system recognises a wide spectrum of pathogens without a need for prior exposure. The main cells responsible are monocytes, macrophages, dendritic cells (DC) and neutrophils phagocytose microbial pathogens triggering a cytokine network resulting in the development of inflammatory and specific immune responses. Findings in the Toll...