scholarly journals The molecular and cellular features of 2-cell-like cells: a reference guide

Development ◽  
2020 ◽  
Vol 147 (16) ◽  
pp. dev189688 ◽  
Author(s):  
Marion Genet ◽  
Maria-Elena Torres-Padilla

ABSTRACTCurrently, two main cell culture models predominate pluripotent stem cell research: embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Thanks to their ability to contribute to and form all tissues within the body, ESCs and iPSCs have proven invaluable in understanding pluripotent states, early embryonic development and cell differentiation, as well as in devising strategies for regenerative medicine. Comparatively little is known about totipotency – a cellular state with greater developmental potential. In mice, only the zygote and the blastomeres of the 2-cell-stage embryo are truly totipotent, as they alone can develop to form the embryo and all of its supportive extra-embryonic tissues. However, the discovery of a rare subpopulation of cells in murine ESC cultures, possessing features of 2-cell embryo blastomeres and expanded cell fate potential, has provided a biochemically tractable model to enable the in vitro study of totipotency. Here, we summarize current known features of these 2-cell-like cells (2CLCs) in an effort to provide a reference for the community, and to clarify what we know about their identity so far.

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Erin A. Kimbrel ◽  
Shi-Jiang Lu

The ability of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) to divide indefinitely without losing pluripotency and to theoretically differentiate into any cell type in the body makes them highly attractive cell sources for large scale regenerative medicine purposes. The current use of adult stem cell-derived products in hematologic intervention sets an important precedent and provides a guide for developing hESC/iPSC based therapies for the blood system. In this review, we highlight biological functions of mature cells of the blood, clinical conditions requiring the transfusion or stimulation of these cells, and the potential for hESC/iPSC-derivatives to serve as functional replacements. Many researchers have already been able to differentiate hESCs and/or iPSCs into specific mature blood cell types. For example, hESC-derived red blood cells and platelets are functional in tasks such as oxygen delivery and blood clotting, respectively and may be able to serve as substitutes for their donor-derived counterparts in emergencies. hESC-derived dendritic cells are functional in antigen-presentation and may be used as off-the-shelf vaccine therapies to stimulate antigen-specific immune responses against cancer cells. However,in vitrodifferentiation systems used to generate these cells will need further optimization before hESC/iPSC-derived blood components can be used clinically.


2019 ◽  
Vol 2 (3) ◽  
pp. 71 ◽  
Author(s):  
Afify ◽  
Chen ◽  
Yan ◽  
Calle ◽  
Nair ◽  
...  

The cancer stem cell (CSC) hypothesis suggests that tumors are sustained exclusively by a small population of the cells with stem cell properties. CSCs have been identified in most tumors and are responsible for the initiation, recurrence, and resistance of different cancers. In vitro CSC models will be of great help in revisiting the mechanism of cancer development, as well as the tumor microenvironment and the heterogeneity of cancer and metastasis. Our group recently described the generation of CSCs from induced pluripotent stem cells (iPSCs), which were reprogrammed from normal cells, and/or embryonic stem cells (ESCs). This procedure will improve the understanding of the essential niche involved in cancer initiation. The composition of this cancer-inducing niche, if identified, will let us know how normal cells convert to malignant in the body and how, in turn, cancer prevention could be achieved. Further, once developed, CSCs demonstrate the ability to differentiate into endothelial cells, cancer-associated fibroblasts, and other phenotypes establishing the CSC niche. These will be good materials for developing novel cancer treatments. In this protocol, we describe how to handle mouse iPSCs/ESCs and how to choose the critical time for starting the conversion into CSCs. This CSC generation protocol is essential for understanding the role of CSC in cancer initiation and progress.


2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3111
Author(s):  
Po-Yu Lin ◽  
Denny Yang ◽  
Chi-Hsuan Chuang ◽  
Hsuan Lin ◽  
Wei-Ju Chen ◽  
...  

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are ‘true’ totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely ‘cluster 3’, as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells.


2016 ◽  
Vol 4 (20) ◽  
pp. 3482-3489 ◽  
Author(s):  
Giuliana E. Salazar-Noratto ◽  
Frank P. Barry ◽  
Robert E. Guldberg

Disease-specific pluripotent stem cells can be derived through genetic manipulation of embryonic stem cells or by reprogramming somatic cells (induced pluripotent stem cells).


Author(s):  
Hao Xu ◽  
Liying Wu ◽  
Guojia Yuan ◽  
Xiaolu Liang ◽  
Xiaoguang Liu ◽  
...  

: Hepatic disease negatively impacts liver function and metabolism. Primary human hepatocytes are the gold standard for the prediction and successful treatment of liver disease. However, the sources of hepatocytes for drug toxicity testing and disease modeling are limited. To overcome this issue, pluripotent stem cells (PSCs) have emerged as an alternative strategy for liver disease therapy. Human PSCs, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can self-renew and give rise to all cells of the body. Human PSCs are attractive cell sources for regenerative medicine, tissue engineering, drug discovery, and developmental studies. Several recent studies have shown that mesenchymal stem cells (MSCs) can also differentiate (or trans-differentiate) into hepatocytes. Differentiation of human PSCs and MSCs into functional hepatocyte-like cells (HLCs) opens new strategies to study genetic diseases, hepatotoxicity, infection of hepatotropic viruses, and analyze hepatic biology. Numerous in vitro and in vivo differentiation protocols have been established to obtain human PSCs/MSCs-derived HLCs and mimic their characteristics. It was recently discovered that microRNAs (miRNAs) play a critical role in controlling the ectopic expression of transcription factors and governing the hepatocyte differentiation of human PSCs and MSCs. In this review, we focused on the role of miRNAs in the differentiation of human PSCs and MSCs into hepatocytes.


2020 ◽  
Author(s):  
Jiaxing Wang ◽  
Ping Long ◽  
Shengnan Tian ◽  
Weihua Zu ◽  
Jing Liu ◽  
...  

Abstract Background Extravillous trophoblast (EVT) cells play an essential role in the maternal-fetal interaction. Although abnormal development and function of EVT cells, including impaired migration and invasion capability, are believed to be etiologically linked to severe pregnancy disorders including pre-eclampsia (PE), the associated molecular mechanisms are not clear ascribed to the lack of an appropriate cell model in vitro. Cyclosporine A (CsA) is a macrolide immunosuppressant and is also used in clinic to improve pregnancy outcomes. However, whether CsA has any effects on the function of EVT cells has not been well investigated. Methods In this study, we induced differentiation of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) into EVT cells (hiPSC-EVT and hESC-EVT cells, respectively) by Y27632, NRG1, A83-01 and matrigel, and collected these derived EVT cells by flow cytometry for sorting cells positive for double HLA-G and KRT7, which are EVT markers. We then investigated the effects of CsA on the invasion and migration of these derived EVT cells. Results We found that the hiPSC-EVT and hESC-EVT cells expressed high levels of the EVT markers such as KRT7, ITGA5 and HLA-G but low levels of OCT4, a stem cell marker, and that CsA significantly promoted the invasion and migration of hiPSC-EVT and hESC-EVT cells. Conclusions We successfully generated hiPSC/hESC-derived human EVT cells, which may be applicable for investigating the remodeling process of spiral arteries remodeling and the possible mechanisms of EVT-related diseases in vitro. Furthermore, our findings provide direct evidence that CsA regulates the function of EVT cells and molecular basis by which CsA may be used to treat pregnancy complications in clinic associated with deficient EVT function.


2020 ◽  
Vol 21 (17) ◽  
pp. 6124
Author(s):  
Clara Sanjurjo-Rodríguez ◽  
Rocío Castro-Viñuelas ◽  
María Piñeiro-Ramil ◽  
Silvia Rodríguez-Fernández ◽  
Isaac Fuentes-Boquete ◽  
...  

Induced pluripotent stem cells (iPSCs) represent an unlimited source of pluripotent cells capable of differentiating into any cell type of the body. Several studies have demonstrated the valuable use of iPSCs as a tool for studying the molecular and cellular mechanisms underlying disorders affecting bone, cartilage and muscle, as well as their potential for tissue repair. Musculoskeletal diseases are one of the major causes of disability worldwide and impose an important socio-economic burden. To date there is neither cure nor proven approach for effectively treating most of these conditions and therefore new strategies involving the use of cells have been increasingly investigated in the recent years. Nevertheless, some limitations related to the safety and differentiation protocols among others remain, which humpers the translational application of these strategies. Nonetheless, the potential is indisputable and iPSCs are likely to be a source of different types of cells useful in the musculoskeletal field, for either disease modeling or regenerative medicine. In this review, we aim to illustrate the great potential of iPSCs by summarizing and discussing the in vitro tissue regeneration preclinical studies that have been carried out in the musculoskeletal field by using iPSCs.


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