scholarly journals 17β-Oestradiol promotes differentiation of human embryonic stem cells into dopamine neurons via cross-talk between insulin-like growth factors-1 and oestrogen receptor β

2017 ◽  
Vol 21 (8) ◽  
pp. 1605-1618 ◽  
Author(s):  
Hong Li ◽  
Chenyue Ding ◽  
Zhi-liang Ding ◽  
Mingfa Ling ◽  
Ting Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Cross Talk ◽  
Oestrogen Receptor ◽  
Embryonic Stem ◽  
Dopamine Neurons ◽  
Insulin Like Growth Factors

scholarly journals Derivation of midbrain dopamine neurons from human embryonic stem cells

2004 ◽  
Vol 101 (34) ◽  
pp. 12543-12548 ◽  
Author(s):  
A. L. Perrier ◽  
V. Tabar ◽  
T. Barberi ◽  
M. E. Rubio ◽  
J. Bruses ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Dopamine Neurons ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells

2000 ◽  
Vol 97 (21) ◽  
pp. 11307-11312 ◽  
Author(s):  
M. Schuldiner ◽  
O. Yanuka ◽  
J. Itskovitz-Eldor ◽  
D. A. Melton ◽  
N. Benvenisty
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem

scholarly journals Craniofacial cartilage organoids from human embryonic stem cells via a neural crest cell intermediate

2021 ◽  
Author(s):  
Lauren E. Foltz ◽  
Tyler Levy ◽  
Anthony Possemato ◽  
Mark L Grimes
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Embryonic Stem Cells ◽  
Cell Signaling ◽  
Neural Crest ◽  
Birth Defects ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Neural Crest Cell ◽  
Chondrocyte Differentiation

Severe birth defects or major injuries to the face require surgical reconstruction and rehabilitation. The ability to make bona fide craniofacial cartilage - cartilage of the head and face - from patient-derived induced pluripotent stem cells (iPSCs) to repair these birth defects and injuries has tremendous translational applications, but is not yet possible. The neural crest is the normal developmental pathway for craniofacial cartilage, however, the knowledge of cell signaling pathways that drive neural crest differentiation into craniofacial chondrocytes is limited. Here we describe a differentiation protocol that generated self-organizing craniofacial cartilage organoids from human embryonic stem cells (hESCs) and IPSCs through a neural crest stem cell (NCSC) intermediate. Histological staining of cartilage organoids revealed tissue architecture typical of hyaline cartilage. Organoids were composed of rounded aggregates of glassy, gray matrix that contained scattered small nuclei in lacunae. Mass spectrometry shows that the organoids express robust levels of cartilage markers including aggrecan, perlecan, proteoglycans, and many collagens. Organoids expressed markers indicative of neural crest lineage, as well as growth factors that are candidates for chondrocyte differentiation factors. The data suggest that chondrocyte differentiation is initiated by autocrine loops driven by a combination of secreted growth factors that bind to chondrocyte receptors. Craniofacial cartilage organoids were continuously cultured for one year, reaching up to one centimeter in diameter. The ability to grow craniofacial cartilage from NCSCs provides insights into the cell signaling mechanisms of differentiation into craniofacial cartilage, which lays the groundwork for understanding mechanistic origins of congenital craniofacial anomalies and repairing cartilaginous structures of the head and face.

Embryonic Erythropoiesis and Definitive Hematopoiesis from Human Embryonic Stem Cells Is Regulated by Cytokines Controlling HSC Growth.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2777-2777
Author(s):  
Elias T. Zambidis ◽  
Bruno Peault ◽  
Fred Bunz ◽  
Curt I. Civin
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Glycophorin A ◽  
Erythroid Cells ◽  
Qrt Pcr ◽  
Primitive Hematopoiesis ◽  
Definitive Hematopoiesis

Abstract Human embryonic stem cells (hESC) provide an invaluable tool for studying the earliest events in human hematopoietic stem cell (HSC) development. We describe novel protocols for the efficient, step-wise differentiation of hESC to embryonic (primitive) erythroid cells and definitive erythro-myeloid cells from embryoid bodies (EB) in semi-solid and liquid cultures. EB cells were re-cultured in semisolid cultures with a cocktail of hematopoietic growth factors at different time points using a modified EB differentiation protocol, and hematopoietic differentiation was analyzed in vitro. The initiation of hematopoiesis, in this model, begins during the first week of EB differentiation. with the formation of primitive macrophages and CD31+/VE-cadherin+ hemato-endothelial clusters that “bud off” primitive embryonic hemoglobin-expressing erythroblasts and multi-potential blast colonies. These clusters ultimately form organized yolk-sac-like structures which produce a loosely adherent primitive hematopoietic cells. After 7–9 days of EB differentiation (prior to CD45 expression), primitive nucleated erythroblast colonies arise and are characterized by a “brilliant red” hemoglobinization under phase microscopy, positivity for embryonic/fetal hemoglobins by Kleihauer-Betke, qRT-PCR assays for epsilon/zeta/gamma chain expression, and a CD71+/glycophorin A+ phenotype. Simultaneously, discrete blast colonies are also shown to develop into mixed multipotential colonies containing secondary erythro-myeloid blast cells, primitive erythroblasts, and macrophages; suggesting a common progenitor for the discrete embryonic phenotypes observed at this stage. Following this first wave of primitive hematopoiesis, definitive CD45+-expressing colony-forming cells (CFC) can be generated from EB cells differentiated for 10–15 days with the sequential appearance of BFU-E, CFU-E, GM-CFC, and multi-lineage CFC. A kinetic expression analysis using qRT-PCR methods, revealed that the first wave of embryonic hematopoiesis at 6–9 days of EB development directly coincides with expression of SCL/TAL1, AML1, GATA1, and GATA2, while the onset of definitive hematopoiesis at 9–15 days directly correlates with increased EB expression of CD34, CD31, CD41, c-myb, and cdx4. In this model, primitive hematopoiesis in EB cells proceeds in the absence of exogenously added growth factors. However, supplementing EB differentiation cultures with FLT3-ligand, KIT-ligand, and THROMBOPOIETIN (FTK), dramatically enhances the number of primitive erythroblast, and multi-lineage blast CFC, as well as the definitive BFU-E, CFU-E, and multi-potent mixed CFC. The kinetics of colony formation for both primitive and definitive CFC is unaffected by FTK supplementation. Moreover, blast cell colonies from EB cells differentiated in the presence of FTK were more potent than those generated without FTK. These blast colonies differentiate into mixed, multi-lineage CD45+/CD13+/CD41+/CD71+/glycophorin A+-expressing colonies that contain both primitive nucleated embryonic hemoglobin-expressing erythroblasts, and definitive mature beta-globin-expressing erythroid cells, neutrophils, monocytes/macrophages, and megakaryocytic precursors. This hESC model reveals the putative existence of a common human progenitor for both embryonic-type and definitive hematopoietic cells, and that cytokines known to expand/self-renew definitive HSC may potentially regulate this differentiation process.

Generation of a Common Progenitor Population from Human Embryonic Stem Cells That Gives Rise to Both Embryonic Erythropoiesis and Definitive Hematopoiesis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 521-521
Author(s):  
Elias T. Zambidis ◽  
Jihan Osborne ◽  
Curt I. Civin
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Regulatory Sequences ◽  
Erythroid Cells ◽  
Definitive Hematopoiesis

Abstract Human embryonic stem cells (hESC) provide a valuable new tool for dissecting the earliest developmental events of human hematopoietic-stem progenitor cell (HSPC) genesis. We have recently reported the efficient step-wise differentiation of hESC to embryonic (primitive) erythroid cells followed by definitive erythro-myeloid hematopoietic cells from human embryoid bodies (hEB). Hematopoiesis proceeds spontaneously from hEB-derived cells and appears to model the earliest events of embryonic and definitive hematopoiesis in a manner resembling human yolk sac development. We now extend our studies to define conditions which may favor differentiation into definitive hematopoietic cells from hEB. We previously demonstrated that hEB-derived primitive hematopoiesis requires fetal calf serum, but proceeds in the absence of supplemented recombinant growth factors to developing hEB’s. We now show that supplementing hEB differentiation cultures with a broad array of hematopoietic growth factors dramatically enhances the number of primitive erythroblasts, definitive myeloid, BFU-E, CFU-E, and multi-potent mixed colonies in methylcellulose CFC assays while not affecting the kinetics of hematopoietic differentiation. The inclusion of VEGF-165 during hEB differentiation was found to have an exceptionally potent effect in increasing the multilineage generation of both primitive and definitive hEB-derived hematopoietic cells. To further define the hEB-derived population which gives rise to primitive and definitive hematopoiesis we FACS-purified a population of CD45-CD31+CD34+ hEB cells which we and others have shown are capable of both endothelial and hematogenous differentiation. Co-culture of this purified population in serum-containing OP9 stromal layers gave rise primarily to definitive-type erythro-myeloid cells including mature beta-globin-expressing erythroid cells, neutrophils, monocytes/macrophages, CD41+ megakaryocyte precursors, and CD56+ NK-like cells. Alternative culture of this purified CD45-CD31+CD34+ hEB population in serum-free, stromal-free cultures supplemented with erythropoietin and VEGF-165 produced an abundant population of embryonic (nucleated gamma, epsilon, zeta chain-hemoglobin-expressing) erythroblasts. To isolate a clonogenic, expandable human hemangioblastic progenitor of primitive and definitive hematopoieisis as well as endothelial cells in our system, we have prepared transgenic hESC lines expressing a GFP reporter cDNA under the hemato-endothelial regulatory sequences of the human genomic SCL/TAL1 locus. Our hESC model reveals, for the first time, the putative existence of a population of human hEB progenitors capable of both embryonic-type and definitive blood cells depending on the differentiation environment.

A simple method for large-scale generation of dopamine neurons from human embryonic stem cells

2010 ◽  
Vol 88 (16) ◽  
pp. 3467-3478 ◽  
Author(s):  
Asuka Morizane ◽  
Vladimer Darsalia ◽  
M. Oktar Guloglu ◽  
Tord Hjalt ◽  
Manolo Carta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Large Scale ◽  
Embryonic Stem ◽  
Dopamine Neurons ◽  
Simple Method
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