Abstract 361: Neuregulin Transcriptional Programming of Embryonic Endothelial Progenitor Cells and Embryonic Stem Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Jijun Hao ◽  
Cristi L Galindo ◽  
Radwan N Safa ◽  
Truc-Linh Tran ◽  
Douglas B Sawyer
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Heart Development ◽  
Progenitor Cell ◽  
Critical Role ◽  
Embryonic Stem ◽  
Mapk Signaling ◽  
P Value ◽  
Type I ◽  
Endothelial Progenitor

Jijun Hao, Cristi L. Galindo, Radwan N. Safa, Truc-Linh Tran, Douglas B. Sawyer Neuregulin-1 (NRG-1) plays a critical role in heart development by signaling through type I receptor tyrosine kinases in the erbB family (erbB2, erbB3 and erbB4). Mice with disrupted expression of NRG-1, ErbB2, ErbB3 or ErbB4 die in utero with failure of cardiac development. We have previously shown that NRG-1 has distinct effects on two embryonic progenitor cell populations that express ErbB2 and ErbB3 receptors. In an embryonic endothelial progenitor cell line (eEPCs) NRG-1 treatment induces phosphorylation of Akt, GSK-3β, and Erk1/2, and protects eEPCs against serum deprivation-induced apoptosis. In embryonic stem cells (ESCs) we find that NRG-1 treatment from day 0∼2 induces cardiomyocyte formation by day 8 in culture, and when ErbB3 is knocked down in the ESCs, NRG-1 fails to promote cardiomyogenesis. To understand early molecular events that might regulate these distinct effects, we analyzed global transcriptional changes induced by NRG-1 in both eEPCs and ESCs using microarrays. There were only 244 significantly differential (p value < 0.05, fold-change > 1.5) genes detected in NRG-1-treated ESCs, while NRG-1 induced differential expression of 1,547 transcripts in eEPCs. Based on functional analysis, the most significantly over-represented function (Fishers Exact Test, p value with FDR < 0.05) in ESCs was “cell morphogenesis during differentiation”. In eEPCs, genes regulated via Ras/MAPK signaling were altered, as were those downstream of the Akt-PI3K pathway and calcium signaling. For both cell lines, the most statistically significant transcription factor identified as a regulator of the genes altered in response to NRG-1 was SRF, consistent with a role for NRG-1 in heart development and regeneration. Based on the results of this study, we constructed a putative signaling pathway whereby NRG mediates cardiomyogenesis in pluripotent stem cells that correlates with phenotypic observations.

Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3065-3075 ◽  
Author(s):  
Olena Klimchenko ◽  
Antonio Di Stefano ◽  
Birgit Geoerger ◽  
Sofiane Hamidi ◽  
Paule Opolon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Fetal Liver ◽  
Critical Role ◽  
Embryonic Stem ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cells

Abstract The early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14lowCD16− precursor to form CD14highCD16+ cells without producing the CD14highCD16− cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.

scholarly journals Perturbations of Heart Development and Function in Cardiomyocytes from Human Embryonic Stem Cells with Trisomy 21

Stem Cells ◽  
2015 ◽  
Vol 33 (5) ◽  
pp. 1434-1446 ◽  
Author(s):  
Alexis Bosman ◽  
Audrey Letourneau ◽  
Laura Sartiani ◽  
Martina Del Lungo ◽  
Flavio Ronzoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Heart Development ◽  
Trisomy 21 ◽  
Embryonic Stem ◽  
And Function

scholarly journals Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Tatsuhito Himeno ◽  
Hideki Kamiya ◽  
Keiko Naruse ◽  
Zhao Cheng ◽  
Sachiko Ito ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Blood Vessels ◽  
Progenitor Cell ◽  
Therapeutic Strategy ◽  
Es Cells ◽  
Embryonic Stem ◽  
Diabetic Polyneuropathy ◽  
Mouse Embryonic Stem Cells ◽  
Intraepidermal Nerve Fiber

Background. Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects. Here, we investigated the efficacy of treatment for diabetic polyneuropathy using angioblast-like cells derived from mouse embryonic stem cells.Methods and Results. Angioblast-like cells were obtained from mouse embryonic stem cells and transplantation of these cells improved several physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve conduction velocities, and reduced blood flow in sciatic nerve and plantar skin. Furthermore, pathologically, the capillary number to muscle fiber ratios were increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve fiber densities were ameliorated in transplanted plantar skin. Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites. Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells.Conclusions. These results suggest that transplantation of angioblast like cells induced from embryonic stem cells appears to be a novel therapeutic strategy for diabetic polyneuropathy.

Long-term, feeder-free maintenance of human embryonic stem cells by mussel-inspired adhesive heparin and collagen type I

2016 ◽  
Vol 32 ◽  
pp. 138-148 ◽  
Author(s):  
Mihyun Lee ◽  
Youngjin Kim ◽  
Ji Hyun Ryu ◽  
Kyuri Kim ◽  
Yong-Mahn Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Collagen Type ◽  
Embryonic Stem ◽  
Collagen Type I ◽  
Type I

scholarly journals Differentiation of embryonic stem cells into fibroblast-like cells in three-dimensional type I collagen gel cultures

2010 ◽  
Vol 47 (2) ◽  
pp. 114-124 ◽  
Author(s):  
Shinsaku Togo ◽  
Tadashi Sato ◽  
Hisatoshi Sugiura ◽  
Xingqi Wang ◽  
Hesham Basma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Type I Collagen ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Collagen Gel ◽  
Type I ◽  
Type I Collagen Gel

scholarly journals Critical role for P53 in regulating the cell cycle of ground state embryonic stem cells

2019 ◽  
Author(s):  
Menno ter Huurne ◽  
Tianran Peng ◽  
Guoqiang Yi ◽  
Guido van Mierlo ◽  
Hendrik Marks ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Ground State ◽  
Critical Role ◽  
Embryonic Stem ◽  
Phase Control ◽  
G1 Phase ◽  
Rna Seq ◽  
Rb Protein ◽  
Uncontrolled Cell Proliferation

AbstractMouse Embryonic Stem Cells (ESCs) grown in serum-supplemented conditions are characterized by an extremely short G1-phase due to the lack of G1-phase control. Concordantly, the G1-phase-specific P53-P21 pathway is compromised in serum ESCs. Here we provide evidence that P53 is activated upon transition of serum ESCs to their pluripotent ground state using serum-free 2i conditions and modulates G1-phase progression. Our data shows that the elongated G1-phase characteristic of ground state ESCs is dependent on P53. RNA-seq and ChIP-seq analyses reveal that P53 directly regulates the expression of the Retinoblastoma (RB) protein and that the hypo-phosphorylated, active RB protein plays a key role in G1-phase control. Our findings suggest that the P53-P21 pathway is active in ground state 2i ESCs and that its role in the G1-checkpoint is abolished in serum ESCs. Taken together, the data reveals a mechanism by which inactivation of P53 can lead to loss of RB and uncontrolled cell proliferation.

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