The article by Gordon Keller, titled "Embryonic stem cell differentiation: emergence of a new era in biology and medicine," published in *Genes & Development* in 2005, reviews the significant advancements in the field of embryonic stem (ES) cell research. ES cells, discovered over two decades ago, have revolutionized biology and medicine by enabling the manipulation of the mouse genome and providing a model for early mammalian development. The review highlights the unique characteristics of ES cells, including their ability to maintain undifferentiated states and generate all cell types in the body. Key aspects of the article include: 1. **Maintaining Undifferentiated ES Cells**: The maintenance of ES cells in culture is discussed, focusing on the role of factors like leukemia inhibitory factor (LIF) and BMP4 in supporting their growth. Recent studies have also identified the importance of transcription factors such as Oct3/4 and nanog in maintaining the undifferentiated state. 2. **Differentiation of ES Cells in Culture**: Three main methods for differentiating ES cells—forming embryoid bodies (EBs), coculture with stromal cells, and monolayer culture—are described. Each method has its advantages and disadvantages, and the review emphasizes the importance of establishing efficient and reproducible differentiation protocols. 3. **Differentiated Cell Types from ES Cells**: The article details the differentiation of mesoderm-derived lineages, including hematopoietic, vascular, and cardiac cells. Hematopoietic development is covered in great detail, highlighting the parallels between ES cell differentiation and early embryonic development. The identification of the hemangioblast, a common progenitor for both hematopoietic and endothelial lineages, is also discussed. 4. **Transplantation of ES-cell-derived Cardiomyocytes**: The potential of ES-cell-derived cardiomyocytes for treating cardiovascular diseases is explored, with studies showing improved cardiac function in animal models following transplantation. The review concludes by outlining the challenges and future directions in ES cell research, emphasizing the need to identify progenitor cells representing the earliest stages of embryonic lineage development. The article underscores the potential of ES cells as a source of cells and tissues for transplantation and the ongoing efforts to understand and control their differentiation.The article by Gordon Keller, titled "Embryonic stem cell differentiation: emergence of a new era in biology and medicine," published in *Genes & Development* in 2005, reviews the significant advancements in the field of embryonic stem (ES) cell research. ES cells, discovered over two decades ago, have revolutionized biology and medicine by enabling the manipulation of the mouse genome and providing a model for early mammalian development. The review highlights the unique characteristics of ES cells, including their ability to maintain undifferentiated states and generate all cell types in the body. Key aspects of the article include: 1. **Maintaining Undifferentiated ES Cells**: The maintenance of ES cells in culture is discussed, focusing on the role of factors like leukemia inhibitory factor (LIF) and BMP4 in supporting their growth. Recent studies have also identified the importance of transcription factors such as Oct3/4 and nanog in maintaining the undifferentiated state. 2. **Differentiation of ES Cells in Culture**: Three main methods for differentiating ES cells—forming embryoid bodies (EBs), coculture with stromal cells, and monolayer culture—are described. Each method has its advantages and disadvantages, and the review emphasizes the importance of establishing efficient and reproducible differentiation protocols. 3. **Differentiated Cell Types from ES Cells**: The article details the differentiation of mesoderm-derived lineages, including hematopoietic, vascular, and cardiac cells. Hematopoietic development is covered in great detail, highlighting the parallels between ES cell differentiation and early embryonic development. The identification of the hemangioblast, a common progenitor for both hematopoietic and endothelial lineages, is also discussed. 4. **Transplantation of ES-cell-derived Cardiomyocytes**: The potential of ES-cell-derived cardiomyocytes for treating cardiovascular diseases is explored, with studies showing improved cardiac function in animal models following transplantation. The review concludes by outlining the challenges and future directions in ES cell research, emphasizing the need to identify progenitor cells representing the earliest stages of embryonic lineage development. The article underscores the potential of ES cells as a source of cells and tissues for transplantation and the ongoing efforts to understand and control their differentiation.