Background and Objectives Endothelial progenitor cells (EPCs) and endothelial cells (ECs) have been applied in the clinic to treat pulmonary arterial hypertension (PAH), a disease characterized by disordered pulmonary vasculature. However, the lack of sufficient transplantable cells before the deterioration of disease condition is a current limitation to apply cell therapy in patients. It is necessary to differentiate pluripotent stem cells (PSCs) into EPCs and identify their characteristics. Methods and Results Comparing previously reported methods of human PSCs-derived ECs, we optimized a highly efficient differentiation protocol to obtain cells that match the phenotype of isolated EPCs from healthy donors. The protocol is compatible with chemically defined medium (CDM), it could produce a large number of clinically applicable cells with low cost. Moreover, we also found PSCs-derived EPCs express CD133, have some characteristics of mesenchymal stem cells and are capable of homing to repair blood vessels in zebrafish xenograft assays. In addition, we further revealed that IPAH PSCs-derived EPCs have higher expression of proliferation-related genes and lower expression of immune-related genes than normal EPCs and PSCs-derived EPCs through microarray analysis. Conclusions In conclusion, we optimized a highly efficient differentiation protocol to obtain PSCs-derived EPCs with the phenotypic and molecular characteristics of EPCs from healthy donors which distinguished them from EPCs from PAH.
Aims Endothelial cells (ECs) have been applied in clinic to treat pulmonary arterial hypertension (PAH), a disease characterized by disordered pulmonary vasculature. However, lack of enough transplantable cells before the deterioration of patient condition is current limitation to apply cell therapy in cardiovascular diseases. So, we thought it necessary to continue to differentiate embryo stem cells (ESCs)/induced-pluripotent stem cells (iPSCs) into endothelial cells (ECs) and identify their characteristics. Methods and results Comparing previous reported methods of human pluripotent cell differentiation toward vascular cells/ Hemogenic Endothelial cells/ endothelial colony-forming cells, we established a highly efficient differentiation protocol to get cells that match phenotype of isolated ECs from health donors. This protocol, including two stages, early mesoderm endothelial progenitor stage and EC marker expression stage. In the first stage, Rock inhibitor Y27632 and DMSO plays an important role in inducing-APLNR + mesoderm and promotes EC differentiation potential; later on SB431542 and BMP4 drives cells toward EC lineage. Meanwhile, an improved protocol with chemically-defined medium (CDM) has similar differentiation efficiency,again demonstrating that a large number of clinically needed cells could be obtained with simple factors. ESC/iPSC-ECs, normal EPCs and IPAH-EPCs have the characteristics of early EPCs marked by CD133 and mesenchymal stem cells. Microarray analysis further revealed IPAH-derived EPCs features of rapid proliferation and weak immune regulation. At last, a model Zebrafish xenograft was utilized to assess the functionality of differentiated ESC/iPSC-ECs. ConclusionsWe established a highly efficient differentiation protocol to get ESC/iPSC-ECs with characteristics of phenotype and molecular matched with early-EPCs from health donors, and revealed the molecular pathogenesis in PAH.
Primed stem cells and naive stem cells are important for understanding early development, but their ribosomes have not been focused on. In this study, we find that big ribosome clusters named Ribo-macs exist in the cytoplasm of naive stem cells. Then, we prove that Ribo-macs are dynamic and physiological in the cytoplasm, and can synthesize proteins associated with biogenesis of endoplasmic reticulum and mitochondria. We also discover and demonstrate that Ribo-macs are the nucleoli, which of significance is promoting us to rethink our understanding of nucleoli. Besides, we reveal that Ribo-macs have a compatible relation with P-bodies and stress granules. In a word, all the results about Ribo-macs provide us with a new insight to understand how cells adapt quickly to environment.
The nuclear mitochondrial DNA (NUMT) is found in cancer cells, but the mitochondrial DNAs entering the nuclei in normal cells have not been captured. Here, we utilized super-resolution optical imaging to capture the phenomenon by the probe PicoGreen and found mitochondrial DNAs and mitochondria accumulated in the nucleoli by four probes and overexpressing the MRPL58-DsRed. Our results provide an new explanation for mtDNA carryover and lay the foundation for the involvement of nuclear export of nucleoli in de novo mitochondrial biogenesis in another of our unpublished articles.
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