scholarly journals A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs

2018 ◽  
Vol 22 (2) ◽  
pp. 235-251.e9 ◽  
Author(s):  
Zheng Wang ◽  
Micah D. Gearhart ◽  
Yu-Wei Lee ◽  
Ishan Kumar ◽  
Bulat Ramazanov ◽  
...  
Keyword(s):  
Human Escs

scholarly journals The Autophagy Gene Atg16L1 is Necessary for Endometrial Decidualization

Endocrinology ◽  
2019 ◽  
Vol 161 (1) ◽  
Author(s):  
Arin K Oestreich ◽  
Sangappa B Chadchan ◽  
Pooja Popli ◽  
Alexandra Medvedeva ◽  
Marina N Rowen ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Implantation Rate ◽  
Conditional Knockout ◽  
Uterine Receptivity ◽  
Placental Development ◽  
Human Escs ◽  
Embryo Survival ◽  
Autophagy Gene ◽  
Decidual Cells

Abstract Uterine receptivity is critical for establishing and maintaining pregnancy. For the endometrium to become receptive, stromal cells must differentiate into decidual cells capable of secreting factors necessary for embryo survival and placental development. Although there are multiple reports of autophagy induction correlated with endometrial stromal cell (ESC) decidualization, the role of autophagy in decidualization has remained elusive. To determine the role of autophagy in decidualization, we utilized 2 genetic models carrying mutations to the autophagy gene Atg16L1. Although the hypomorphic Atg16L1 mouse was fertile and displayed proper decidualization, conditional knockout in the reproductive tract of female mice reduced fertility by decreasing the implantation rate. In the absence of Atg16L1, ESCs failed to properly decidualize and fewer blastocysts were able to implant. Additionally, small interfering RNA knock down of Atg16L1 was detrimental to the decidualization response of human ESCs. We conclude that Atg16L1 is necessary for decidualization, implantation, and overall fertility in mice. Furthermore, considering its requirement for human endometrial decidualization, these data suggest Atg16L1 may be a potential mediator of implantation success in women.

scholarly journals Function of Pumilio Genes in Human Embryonic Stem Cells and Their Effect in Stemness and Cardiomyogenesis

2019 ◽  
Author(s):  
Isabelle Leticia Zaboroski Silva ◽  
Anny Waloski Robert ◽  
Guillermo Cabrera Cabo ◽  
Lucia Spangenberg ◽  
Marco Augusto Stimamiglio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Embryonic Stem ◽  
Mrna Levels ◽  
Human Escs ◽  
Mrna Targets ◽  
Cardiomyogenic Differentiation

AbstractPosttranscriptional regulation plays a fundamental role in the biology of embryonic stem cells (ESCs). Many studies have demonstrated that multiple mRNAs are coregulated by one or more RNA binding proteins (RBPs) that orchestrate the expression of these molecules. A family of RBPs, known as PUF (Pumilio-FBF), is highly conserved among species and has been associated with the undifferentiated and differentiated states of different cell lines. In humans, two homologs of the PUF family have been found: Pumilio 1 (PUM1) and Pumilio 2 (PUM2). To understand the role of these proteins in human ESCs (hESCs), we first demonstrated the influence of the silencing of PUM1 and PUM2 on pluripotency genes. OCT4 and NANOG mRNA levels decreased significantly with the knockdown of Pumilio, suggesting that PUMILIO proteins play a role in the maintenance of pluripotency in hESCs. Furthermore, we observed that the hESCs silenced for PUM1 and 2 exhibited an improvement in efficiency of in vitro cardiomyogenic differentiation. Using in silico analysis, we identified mRNA targets of PUM1 and PUM2 expressed during cardiomyogenesis. With the reduction of PUM1 and 2, these target mRNAs would be active and could be involved in the progression of cardiomyogenesis.

scholarly journals Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 261 ◽  
Author(s):  
Sergey Sinenko ◽  
Elena Skvortsova ◽  
Mikhail Liskovykh ◽  
Sergey Ponomartsev ◽  
Andrey Kuzmin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Biomedical Applications ◽  
Fluorescent Protein ◽  
Leukemia Virus ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Human Artificial Chromosome ◽  
Human Escs ◽  
Human Ipscs ◽  
Induced Pluripotent

AlphoidtetO-type human artificial chromosome (HAC) has been recently synthetized as a novel class of gene delivery vectors for induced pluripotent stem cell (iPSC)-based tissue replacement therapeutic approach. This HAC vector was designed to deliver copies of genes into patients with genetic diseases caused by the loss of a particular gene function. The alphoidtetO-HAC vector has been successfully transferred into murine embryonic stem cells (ESCs) and maintained stably as an independent chromosome during the proliferation and differentiation of these cells. Human ESCs and iPSCs have significant differences in culturing conditions and pluripotency state in comparison with the murine naïve-type ESCs and iPSCs. To date, transferring alphoidtetO-HAC vector into human iPSCs (hiPSCs) remains a challenging task. In this study, we performed the microcell-mediated chromosome transfer (MMCT) of alphoidtetO-HAC expressing the green fluorescent protein into newly generated hiPSCs. We used a recently modified MMCT method that employs an envelope protein of amphotropic murine leukemia virus as a targeting cell fusion agent. Our data provide evidence that a totally artificial vector, alphoidtetO-HAC, can be transferred and maintained in human iPSCs as an independent autonomous chromosome without affecting pluripotent properties of the cells. These data also open new perspectives for implementing alphoidtetO-HAC as a gene therapy tool in future biomedical applications.

scholarly journals Doxycycline supplementation allows for the culture of human ESCs/iPSCs with media changes at 3-day intervals

2015 ◽  
Vol 15 (3) ◽  
pp. 608-613 ◽  
Author(s):  
Mi-Yoon Chang ◽  
Boram Oh ◽  
Yong-Hee Rhee ◽  
Sang-Hun Lee
Keyword(s):  
Human Escs

Sequential Genetic Modification of the hprt Locus in Human ESCs Combining Gene Targeting and Recombinase-Mediated Cassette Exchange

2008 ◽  
Vol 10 (2) ◽  
pp. 217-230 ◽  
Author(s):  
Alexandra I. Di Domenico ◽  
Ioannis Christodoulou ◽  
Steve C. Pells ◽  
Jim McWhir ◽  
Alison J. Thomson
Keyword(s):  
Gene Targeting ◽  
Genetic Modification ◽  
Human Escs ◽  
Cassette Exchange ◽  
Hprt Locus

Exploring early differentiation and pluripotency in domestic animals

2017 ◽  
Vol 29 (1) ◽  
pp. 101 ◽  
Author(s):  
R. Michael Roberts ◽  
Ye Yuan ◽  
Toshihiko Ezashi
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Short Review ◽  
Potential Usefulness ◽  
Meat Production ◽  
Human Escs ◽  
Domestic Species

This short review describes some general features of the origins of the pluripotent inner cell mass and epiblast during the early development of eutherian mammals and the two kinds of embryonic stem cell (ESC), naïve and primed type, that have been produced from these structures. We point out that the derivation of pluripotent stem cells from domesticated species continues to be fraught with difficulties, most likely because the culture requirements of these cells are distinct from those of mouse and human ESCs. Generation of induced pluripotent stem cells (iPSCs) from the domesticated species has been more straightforward, although the majority of the iPSC lines remain dependent on the continued expression of one or more integrated reprogramming genes. Although hope for the potential usefulness of these cells in genetic modification of livestock and other domestic species has dimmed, ESCs and iPSCs remain our best source of self-renewing populations of pluripotent cells, with potential usefulness in preserving and propagating valuable animal breeds and making contributions to fields such as regenerative medicine, toxicology and even laboratory meat production.

scholarly journals PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs

2020 ◽  
Vol 26 (2) ◽  
pp. 294
Author(s):  
Zhexin Zhu ◽  
Chunliang Li ◽  
Yanwu Zeng ◽  
Jianyi Ding ◽  
Zepeng Qu ◽  
...  
Keyword(s):  
Human Escs ◽  
Metabolic Circuit

scholarly journals Wilms tumor 1 regulates lipid accumulation in human endometrial stromal cells during decidualization

2020 ◽  
Vol 295 (14) ◽  
pp. 4673-4683 ◽  
Author(s):  
Isao Tamura ◽  
Haruka Takagi ◽  
Yumiko Doi-Tanaka ◽  
Yuichiro Shirafuta ◽  
Yumiko Mihara ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Lipid Accumulation ◽  
Wilms Tumor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Escs ◽  
Endometrial Stromal Cells ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Uptake ◽  
Wilms Tumor 1

We previously reported that the transcription factor Wilms tumor 1 (WT1) regulates the expression of insulin-like growth factor-binding protein-1 (IGFBP-1) and prolactin (PRL) during decidualization of human endometrial stromal cells (ESCs). However, other roles of WT1 in decidualization remain to be fully clarified. Here, we investigated how WT1 regulates the physiological functions of human ESCs during decidualization. We incubated ESCs isolated from proliferative-phase endometrium with cAMP to induce decidualization, knocked down WT1 with siRNA, and generated three types of treatments (nontreated cells, cAMP-treated cells, and cAMP-treated + WT1-knockdown cells). To identify WT1-regulated genes, we used gene microarrays and compared the transcriptome data obtained among these three treatments. We observed that WT1 up-regulates 121 genes during decidualization, including several genes involved in lipid transport. The WT1 knockdown inhibited lipid accumulation (LA) in the cAMP-induced ESCs. To examine the mechanisms by which WT1 regulates LA, we focused on very low-density lipoprotein receptor (VLDLR), which is involved in lipoprotein uptake. We found that cAMP up-regulates VLDLR and that the WT1 knockdown inhibits it. Results of ChIP assays revealed that cAMP increases the recruitment of WT1 to the promoter region of the VLDLR gene, indicating that WT1 regulates VLDLR expression. Moreover, VLDLR knockdown inhibited cAMP-induced LA, and VLDLR overexpression reverted the suppression of LA caused by the WT1 knockdown. Taken together, our results indicate that WT1 enhances lipid storage by up-regulating VLDLR expression in human ESCs during decidualization.

scholarly journals Generation of Transplantable Striatal Projection Neurons from Human ESCs

2012 ◽  
Vol 10 (4) ◽  
pp. 349-350 ◽  
Author(s):  
Malin Parmar ◽  
Anders Björklund
Keyword(s):  
Projection Neurons ◽  
Human Escs ◽  
Striatal Projection Neurons
Sign in / Sign up

Export Citation Format

Share Document