scholarly journals Commitment of embryonic stem cells to an epidermal cell fate and differentiation in vitro

2005 ◽  
Vol 232 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Tammy-Claire Troy ◽  
Kursad Turksen
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Epidermal Cell ◽  
Embryonic Stem

scholarly journals Morphogen And Community Effects Determine Cell Fates In Response To BMP4 Signaling In Human Embryonic Stem Cells

2017 ◽  
Author(s):  
Anastasiia Nemashkalo ◽  
Albert Ruzo ◽  
Idse Heemskerk ◽  
Aryeh Warmflash
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Community Effects ◽  
Cell Fates ◽  
Standard Culture

AbstractParacrine signals maintain developmental states and create cell-fate patterns in vivo, and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro. Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells (“μColonies”) to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in μColonies and standard culture conditions and find that in μColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions, BMP4 acts as morphogen, but this effect requires secondary signals and particular cell densities. We further find that a “community effect” enforces a common fate within μColonies both in the state of pluripotency and when cells are differentiated, and that this effect allows more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation.Summary StatementWe quantitatively examined signaling and differentiation in hESC colonies of varying size treated with BMP4. We show that secondary signals result in morphogen and community effects that determine cell fates.

scholarly journals Bdh2 Deficiency Promotes Endoderm-Biased Early Differentiation of Mouse Embryonic Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuting Fu ◽  
Fangyuan Liu ◽  
Shuo Cao ◽  
Jia Zhang ◽  
Huizhi Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Iron Homeostasis ◽  
Embryonic Stem ◽  
Cell Fate Decisions ◽  
Rate Limiting Step ◽  
Fate Decision

3-hydroxybutyrate dehydrogenase-2 (Bdh2), a short-chain dehydrogenase, catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore, playing a key role in iron homeostasis, energy metabolism and apoptosis. However, the function of Bdh2 in embryonic stem cells (ESCs) remains unknown. To gain insights into the role of Bdh2 on pluripotency and cell fate decisions of mouse ESCs, we generated Bdh2 homozygous knockout lines for both mouse advanced embryonic stem cell (ASC) and ESC using CRISPR/Cas9 genome editing technology. Bdh2 deficiency in both ASCs and ESCs had no effect on expression of core pluripotent transcription factors and alkaline phosphatase activity, suggesting dispensability of Bdh2 for self-renewal and pluripotency of ESCs. Interestingly, cells with Bdh2 deficiency exhibited potency of endoderm differentiation in vitro; with upregulated endoderm associated genes revealed by RNA-seq and RT-qPCR. We further demonstrate that Bdh2 loss inhibited expression of multiple methyltransferases (DNMTs) at both RNA and protein level, suggesting that Bdh2 may be essentially required to maintain DNA methylation in ASCs and ESCs. Overall, this study provides valuable data and resources for understanding how Bdh2 regulate earliest cell fate decision and DNA methylation in ASCs/ESCs.

VEGF-A165 augments erythropoietic development from human embryonic stem cells

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2504-2512 ◽  
Author(s):  
Chantal Cerdan ◽  
Anne Rouleau ◽  
Mickie Bhatia
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Human Embryonic Stem Cells ◽  
Embryoid Body ◽  
Embryonic Stem ◽  
Vascular Endothelial ◽  
Erythroid Progenitor ◽  
Endothelial Growth Factor

Abstract Combinations of hematopoietic cytokines and the ventral mesoderm inducer BMP-4 have recently been shown to augment hematopoietic cell fate of human embryonic stem cells (hESCs) during embryoid body (EB) development. However, factors capable of regulating lineage commitment of hESC-derived hematopoiesis have yet to be reported. Here we show that vascular endothelial growth factor (VEGF-A165) selectively promotes erythropoietic development from hESCs. Effects of VEGF-A165 were dependent on the presence of hematopoietic cytokines and BMP-4, and could be augmented by addition of erythropoietin (EPO). Treatment of human EBs with VEGF-A165 increased the frequency of cells coexpressing CD34 and the VEGF-A165 receptor KDR, as well as cells expressing erythroid markers. Although fetal/adult globins were unaffected, VEGF-A165 induced the expression of embryonic zeta (ζ) and epsilon (ϵ) globins, and was accompanied by expression of the hematopoietic transcription factor SCL/Tal-1. In addition to promoting erythropoietic differentiation from hESCs, the presence of VEGF-A165 enhanced the in vitro self-renewal potential of primitive hematopoietic cells capable of erythroid progenitor capacity. Our study demonstrates a role for VEGF-A165 during erythropoiesis of differentiating hESCs, thereby providing the first evidence for a factor capable of regulating hematopoietic lineage development of hESCs.

scholarly journals Endogenous auxin directs development of embryonic stem cells into somatic proembryos in Arabidopsis

2021 ◽  
Author(s):  
Remko Offringa ◽  
Omid Karami ◽  
Cheryl Philipsen ◽  
Arezoo Rahimi ◽  
Annisa Ratna Nurillah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Auxin Biosynthesis ◽  
Dichlorophenoxyacetic Acid ◽  
Embryonic Cells ◽  
Development And Differentiation ◽  
2,4 Dichlorophenoxyacetic Acid

Somatic embryogenesis (SE) is the process by which embryos develop from in vitro cultured vegetative tissue explants. The synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used for SE induction, but SE can also be induced by overexpression of specific transcription factors, such as AT-HOOK MOTIF NUCLEAR LOCALIZED 15 (AHL15). 2,4-D and AHL15 both trigger the biosynthesis of the natural auxin indole-3-acetic acid (IAA). However, the role of this endogenously produced auxin in SE is yet not well understood. In this study we show that the induction of embryonic stem cells from explants does not require IAA biosynthesis, whereas an increase in IAA levels is essential to maintain embryo identity and for embryo formation from these stem cells. Further analysis showed that YUCCA (YUC) genes involved in the IPyA auxin biosynthesis pathway are up-regulated in embryo-forming tissues. Chemical inhibition of the IPyA pathway significantly reduced or completely inhibited the formation of somatic embryos in both 2,4-D-and AHL15-dependent systems. In the latter system, SE could be restored by exogenous IAA application, confirming that the biosynthesis-mediated increase in IAA levels is important. Our analyses also show that PIN1 and AUX1 are the major auxin carriers that determine respectively auxin efflux and influx during SE. This auxin transport machinery is required for the proper transition of embryonic cells to proembryos and, later, for correct cell fate specification and differentiation. Taken together, our results indicate that auxin biosynthesis in conjunction with its polar transport are required during SE for multicellular somatic proembryo development and differentiation.

scholarly journals Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

2021 ◽  
Author(s):  
Eun-Young Shin ◽  
Seah Park ◽  
Won Yun Choi ◽  
Dong Ryul Lee
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Male Hypogonadism ◽  
Testosterone Levels ◽  
Sequence Of Events ◽  
Short Period ◽  
Molecular Compounds

Abstract Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

scholarly journals Creation of Engineered Cardiac Tissue In Vitro From Mouse Embryonic Stem Cells

Circulation ◽  
2006 ◽  
Vol 113 (18) ◽  
pp. 2229-2237 ◽  
Author(s):  
Xi-Min Guo ◽  
Yun-Shan Zhao ◽  
Hai-Xia Chang ◽  
Chang-Yong Wang ◽  
Ling-Ling E ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cardiac Tissue ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells
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