APELIN promotes hematopoiesis from human embryonic stem cells

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. 6243-6254 ◽  
Author(s):  
Qing C. Yu ◽  
Claire E. Hirst ◽  
Magdaline Costa ◽  
Elizabeth S. Ng ◽  
Jacqueline V. Schiesser ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Transcriptional Profiling ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Peptide Ligand ◽  
The Media ◽  
Apelin Receptor

Abstract Transcriptional profiling of differentiating human embryonic stem cells (hESCs) revealed that MIXL1-positive mesodermal precursors were enriched for transcripts encoding the G-protein–coupled APELIN receptor (APLNR). APLNR-positive cells, identified by binding of the fluoresceinated peptide ligand, APELIN (APLN), or an anti-APLNR mAb, were found in both posterior mesoderm and anterior mesendoderm populations and were enriched in hemangioblast colony-forming cells (Bl-CFC). The addition of APLN peptide to the media enhanced the growth of embryoid bodies (EBs), increased the expression of hematoendothelial genes in differentiating hESCs, and increased the frequency of Bl-CFCs by up to 10-fold. Furthermore, APLN peptide also synergized with VEGF to promote the growth of hESC-derived endothelial cells. These studies identified APLN as a novel growth factor for hESC-derived hematopoietic and endothelial cells.

Assessment of Differentiation Aspects by the Morphological Classification of Embryoid Bodies Derived from Human Embryonic Stem Cells

2011 ◽  
Vol 20 (11) ◽  
pp. 1925-1935 ◽  
Author(s):  
Jung Mo Kim ◽  
Sung-Hwan Moon ◽  
Sung Geum Lee ◽  
Youn Jeong Cho ◽  
Ki Sung Hong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Morphological Classification

Embryoid Bodies–Based Multilineage Differentiation of Human Embryonic Stem Cells Grown on Feeder-Free Conditions

2021 ◽  
Author(s):  
Luciana Isaja ◽  
Sofía Luján Ferriol-Laffouillere ◽  
Sofía Mucci ◽  
María Soledad Rodríguez-Varela ◽  
Leonardo Romorini
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Multilineage Differentiation

Transcriptional profiling of initial differentiation events in human embryonic stem cells

2004 ◽  
Vol 323 (2) ◽  
pp. 453-464 ◽  
Author(s):  
John D. Calhoun ◽  
Raj R. Rao ◽  
Susanne Warrenfeltz ◽  
Romdhane Rekaya ◽  
Stephen Dalton ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Transcriptional Profiling ◽  
Embryonic Stem

scholarly journals Definitive hematopoietic stem/progenitor cells from human embryonic stem cells through serum/feeder-free organoid-induced differentiation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Selami Demirci ◽  
Juan J. Haro-Mora ◽  
Alexis Leonard ◽  
Claire Drysdale ◽  
Daniela Malide ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Close Association ◽  
Embryonic Stem ◽  
Precursor Cells ◽  
Embryoid Bodies ◽  
Confocal Imaging ◽  
Hematopoietic Stem ◽  
Tcr Repertoire

Abstract Background Ex vivo production of hematopoietic stem/precursor cells (HSPCs) represents a promising versatile approach for blood disorders. Methods To derive definitive HSPCs from human embryonic stem cells (ESCs), we differentiated mesodermally specified embryoid bodies (EBs) on gelatin-coated plates in serum/feeder-free conditions. Results Seven-day EB maturation followed by an 8-day differentiation period on OP9 cells provided the highest number of definitive (CD34+ CD235a−, 69%, p < 0.01) and lowest number of primitive (CD34− CD235a+, 1.55%, p < 0.01) precursor cells along with the highest colony-forming units (149.8 ± 11.6, p < 0.01) in feeder-free conditions. Maximal HSPC fraction (CD34+ CD38− CD45RA− CD49f+ CD90+) was 7.6–8.9% after 10 days of hematopoietic differentiation with 14.5% adult β-globin expression following RBC differentiation. Myeloid and erythroid colonies were restricted strictly to the CD34+ CD43+ fraction (370.5 ± 65.7, p < 0.001), while the CD34− CD43+ fraction produced only a small number of colonies (21.6 ± 11.9). In addition, we differentiated the CD34+ CD43+ cells towards T-lymphocytes using the OP9/DLL1 co-culture system demonstrating double-positive T cells (CD4+ CD8+) with CD3+ expression displaying a broad T cell receptor (TCR) repertoire. Confocal imaging of organoid-like structures revealed a close association of CD31+ cells with CD34+ and CD43+ cells, suggesting a potential emergence of HSPCs through endothelial to hematopoietic transition. Furthermore, fluorescently labeled organoids exhibited the emergence of spherical non-attached cells from rare progenitors at the border of the organoid center. Conclusions In summary, definitive HSPCs can be derived from ESCs through a dynamic cellular process from an organoid-like structure, where erythroid progeny are capable of producing adult hemoglobin and lymphoid progeny shows a diverse TCR repertoire.

scholarly journals Differentiation of Human Embryonic Stem Cells into Embryoid Bodies Comprising the Three Embryonic Germ Layers

2000 ◽  
Vol 6 (2) ◽  
pp. 88-95 ◽  
Author(s):  
Joseph Itskovitz-Eldor ◽  
Maya Schuldiner ◽  
Dorit Karsenti ◽  
Amir Eden ◽  
Ofra Yanuka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Germ Layers

scholarly journals Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 122-131 ◽  
Author(s):  
Petter S. Woll ◽  
Julie K. Morris ◽  
Matt S. Painschab ◽  
Rebecca K. Marcus ◽  
Aimee D. Kohn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Human Embryonic Stem Cells ◽  
Stromal Cells ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Human embryonic stem cells (hESCs) provide an important means to effectively study soluble and cell-bound mediators that regulate development of early blood and endothelial cells in a human model system. Here, several complementary methods are used to demonstrate canonical Wnt signaling is important for development of hESC-derived cells with both hematopoietic and endothelial potential. Analyses using both standard flow cy-tometry, as well the more detailed high-throughput image scanning flow cytometry, characterizes sequential development of distinct early developing CD34brightCD31+Flk1+ cells and a later population of CD34dimCD45+ cells. While the CD34brightCD31+Flk1+ have a more complex morphology and can develop into both endothelial cells and hematopoietic cells, the CD34dimCD45+ cells have a simpler morphology and give rise to only hematopoietic cells. Treatment with dickkopf1 to inhibit Wnt signaling results in a dramatic decrease in development of cells with hematoendothelial potential. In addition, activation of the canonical Wnt signaling pathway in hESCs by coculture with stromal cells that express Wnt1, but not use of noncanonical Wnt5-expressing stromal cells, results in an accelerated differentiation and higher percentage of CD34brightCD31+Flk1+ cells at earlier stages of differentiation. These studies effectively demonstrate the importance of canonical Wnt signaling to mediate development of early hematoendothelial progenitors during human development.

scholarly journals RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells

Blood ◽  
2013 ◽  
Vol 121 (15) ◽  
pp. 2882-2890 ◽  
Author(s):  
Dan Ran ◽  
Wei-Jong Shia ◽  
Miao-Chia Lo ◽  
Jun-Bao Fan ◽  
David A. Knorr ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ex Vivo ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Lineage Commitment ◽  
Hematopoietic Differentiation

Abstract Advancements in human pluripotent stem cell (hPSC) research have potential to revolutionize therapeutic transplantation. It has been demonstrated that transcription factors may play key roles in regulating maintenance, expansion, and differentiation of hPSCs. In addition to its regulatory functions in hematopoiesis and blood-related disorders, the transcription factor RUNX1 is also required for the formation of definitive blood stem cells. In this study, we demonstrated that expression of endogenous RUNX1a, an isoform of RUNX1, parallels with lineage commitment and hematopoietic emergence from hPSCs, including both human embryonic stem cells and inducible pluripotent stem cells. In a defined hematopoietic differentiation system, ectopic expression of RUNX1a facilitates emergence of hematopoietic progenitor cells (HPCs) and positively regulates expression of mesoderm and hematopoietic differentiation-related factors, including Brachyury, KDR, SCL, GATA2, and PU.1. HPCs derived from RUNX1a hPSCs show enhanced expansion ability, and the ex vivo–expanded cells are capable of differentiating into multiple lineages. Expression of RUNX1a in embryoid bodies (EBs) promotes definitive hematopoiesis that generates erythrocytes with β-globin production. Moreover, HPCs generated from RUNX1a EBs possess ≥9-week repopulation ability and show multilineage hematopoietic reconstitution in vivo. Together, our results suggest that RUNX1a facilitates the process of producing therapeutic HPCs from hPSCs.

scholarly journals Neuroprotective Effects of Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells in Transient Focal Cerebral Ischemia in Rats

2009 ◽  
Vol 29 (4) ◽  
pp. 780-791 ◽  
Author(s):  
Yi-Ping Liu ◽  
Hakan Seçkin ◽  
Yusuf İzci ◽  
Zhong Wei Du ◽  
Yi-Ping Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Embryonic Stem Cells ◽  
Cerebral Ischemia ◽  
Human Embryonic Stem Cells ◽  
Focal Cerebral Ischemia ◽  
Embryonic Stem ◽  
Transient Focal Cerebral Ischemia ◽  
Infarction Volume

Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for β-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia.

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