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Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification.
Abstract: Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor β (TGF-β), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro and are capable of contributing to intra- or inter-species chimeras in vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication Date: 2020-12-02 PubMed ID: 33271070DOI: 10.1016/j.stem.2020.11.003Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The researchers found a method to derive pluripotent stem cells (PSCs), named XPSCs, from mice, horses, and humans that can become primordial germ cell-like cells in the lab, and contribute to chimeras (blended organisms) in living environments. This discovery may greatly advance the study of mammalian pluripotency and the development of new biomedical treatments.
Understanding the Research
This research focusses on pluripotent stem cells (PSCs), which are cells that have the capability to develop into any type of cell in the body. The multi-state adaptability of these cells is also referred to as the “pluripotency continuum”.
- The researchers noted that while several types of PSCs have been generated so far, none have exhibited the ability to form chimeras and respond to primordial germ cell (PGC) specifications simultaneously. These two features are characteristics of formative pluripotency, an intermediate state of the pluripotency spectrum.
- To obtain these versatile PSCs, the researchers manipulated several key molecular pathways involving fibroblast growth factor (FGF), transforming growth factor β (TGF-β), and WNT. The resultant cells, which they named XPSCs, demonstrated the desired dual competency.
- This was proven through experiments where the XPSCs could be induced to form PGC-like cells under lab conditions, and also contribute to chimeras (combination of cells from two different species) in a living environment.
Significance of the Research
The discovery of the XPSCs holds significant implications for biomedical research and treatment methods.
- By serving as an intermediate state between naive and primed pluripotency, XPSCs provide new opportunities to study and understand the dynamics of pluripotency in mammalian cells.
- Research on the molecular mechanisms that govern PGC specification can gain new insights from studying the transformation of XPSCs into PGC-like cells. This could have significant implications for reproductive health and treatments.
- The methodology for deriving XPSCs can possibly be applied to other mammalian species, thereby potentially broadening the scope and utility of pluripotent stem cells in biomedical applications across different species.
Cite This Article
APA
Yu L, Wei Y, Sun HX, Mahdi AK, Pinzon Arteaga CA, Sakurai M, Schmitz DA, Zheng C, Ballard ED, Li J, Tanaka N, Kohara A, Okamura D, Mutto AA, Gu Y, Ross PJ, Wu J.
(2020).
Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification.
Cell Stem Cell, 28(3), 550-567.e12.
https://doi.org/10.1016/j.stem.2020.11.003 Publication
Researcher Affiliations
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China; International Healthcare Innovation Institute, Jiangmen 529040, China.
- Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
- Department of Animal Science, University of California, Davis, Davis, CA 95616, USA.
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
- Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan.
- Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan.
- Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan.
- Instituto de Investigaciones Biotecnológicas IIB-INTECH Dr. Rodolfo Ugalde, UNSAM-CONICET, Buenos Aires 1650, Argentina.
- Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
- Department of Animal Science, University of California, Davis, Davis, CA 95616, USA.
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: jun2.wu@utsouthwestern.edu.
MeSH Terms
- Animals
- Cell Differentiation
- Chimera
- Germ Cells
- Horses
- Mice
- Pluripotent Stem Cells
Conflict of Interest Statement
Declaration of Interests L.Y. and J.W. are inventors on a patent application arising from this work. The other authors declare no competing interests.
Citations
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