Harnessing the potential of induced pluripotent stem cells for regenerative medicine. From teratocarcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research. Pluripotency in the embryo and in culture. Control of the embryonic stem cell state. It initiated a race to reprogram human fibroblasts to pluripotency, leading to widespread accessibility to pluripotent stem cells. A landmark paper that demonstrates transcription factor-based reprogramming to pluripotent-like cells. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. The isolation and properties of a clonal tissue culture strain of pluripotent mouse teratoma cells. Developmental potentialities of clonal in vitro cultures of mouse testicular teratoma. It remains unclear whether gene expression heterogeneity within a clonal pluripotent stem cell line is a crucial feature of pluripotency, and whether this gene expression heterogeneity is associated with functional differences between different pluripotent cell lines. Most genetic differences between founder and reprogrammed cells seem to pre-exist in a minor population of the founder cells.Įpigenetic differences between ES cells and iPS cells are both residual (that is, they maintain the same epigenetic state as their respective founder cell type) and aberrant (that is, resembling neither ES cells nor founder cells), and both types of differences may have an impact on the in vitro differentiation process. This suggests that genetic or epigenetic changes are silent in the pluripotent state. Pluripotent stem cells derived using the same method have highly similar gene expression profiles, yet can exhibit functional differences. In some cases, the differences can be ameliorated by altering culture conditions by adding or removing specific growth factors and/or signalling molecules. The molecular underpinnings of these functional differences are unclear. These differences currently limit their possible application in the clinic and as a research tool. This model might also clarify the molecular mechanism behind certain disorders, for example atherosclerotic lesions.There are marked differences in the in vitro differentiation capacity of pluripotent stem cell lines, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. ![]() Each lineage serves as a powerful regenerative tool, including treatment for hemoglobinopathies (anemia, thalassemia), thrombocytopenia, leukocyte and immunodeficient-related diseases. In lymphoid lineage, CLP will further differentiate into B-cell and T-cell and natural killer (NK) cell progenitors, with a final commitment to mature B cells, T cells and NK cells. In myeloid lineage, CMP will further divide into megakaryocyte–erythroid progenitor (MEP) and granulocyte/monocyte progenitor (GMP), finally committing to mature blood cells comprising of erythrocytes, megakaryocyte → platelets, monocyte → macrophages and granulocytes (neutrophils, eosinophils, basophils). After pre-hematopoietic stem cells (HSCs) commit to mature HSCs, multipotent progenitor (MPP) cells are generated with the potential to further differentiate into two major lineages: common myeloid progenitor (CMP) and common lymphoid progenitor (CLP). ![]() Schematic representations of each hematopoietic cell lineage with respect to their applications and disease-treatment potentials. ![]() We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system.
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