scholarly journals An in vitro stem cell model of human epiblast and yolk sac interaction

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kirsty ML Mackinlay ◽  
Bailey AT Weatherbee ◽  
Viviane Souza Rosa ◽  
Charlotte E Handford ◽  
George Hudson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Human Embryo ◽  
Cell Model ◽  
Embryonic Stem ◽  
Yolk Sac ◽  
Embryonic Cells ◽  
Post Implantation

Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.

scholarly journals Patentability of the Human Embryonic Stem Cell Lines: A Legal and Ethical Aspect

2020 ◽  
Author(s):  
Tansu Sayar Kanyış ◽  
Ezgi Arslan ◽  
Oğuzhan Kanyış
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Lines ◽  
Human Embryo ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Point Of View ◽  
Stem Cell Lines

In this study, patentability of the human embryonic stem cell lines has discussed in the legal and ethical perspectives. In vitro human embryonic stem cells can be defined as body parts that are departed from the body. Human embryonic stem cell lines are constituted of differentiated self-renewal pluripotent stem cells, which means they have no characteristics to become a human-being. However, interpreting the terms like human embryo and right to property widely can cause the human embryonic stem cell lines are misunderstood as unpatentable. For our point of view, giving the human embryo the protections of both personal rights of the donor and the right to property of the owner of the invention does not reduce the legal/moral status of the human embryo. Besides, the obligations which these rights imposes to their owners, such as the principle of human dignity and prohibition of financial gain can protect the human embryo in a better way.

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.

Epidermal cell lineage

1998 ◽  
Vol 76 (6) ◽  
pp. 889-898 ◽  
Author(s):  
Kursad Turksen ◽  
Tammy-Claire Troy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Skin Diseases ◽  
Cell Model ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Model System ◽  
Epidermal Stem Cells ◽  
Lineage Differentiation

The epidermis is a stratified squamous epithelium, which is under a constant state of proliferation, commitment, differentiation, and elimination so that the functional integrity of the tissue is maintained. The intact epidermis has the ability to respond to diverse environmental stimuli by continuous turnover to maintain its normal homeostasis throughout an organism's life. This is achieved by a tightly regulated balance between stem cell self-renewal and the generation of a population of cells that undergo a limited number of more rapid (amplifying) transit divisions before giving rise to nonproliferative, terminally differentiating cells. This process makes it an excellent model system to study lineage, commitment, and differentiation, although neither the identity of epidermal stem cells nor the precise steps and regulators that lead to mature epidermal cells have yet been determined. Furthermore, the identities of genes that initiate epidermal progenitor commitment to the epidermal lineage, from putative epidermal stem cells, are unknown. This is mainly due to the lack of an in vitro model system, as well as the lack of specific reagents, to study the early events in epidermal lineage. Our recent development of a differentiating embryonic stem cell model for epidermal lineage now offers the opportunity to analyze the factors that regulate epidermal lineage. These studies will provide new insight into epidermal lineage and lead to a better understanding of various hyperproliferative skin diseases such as psoriasis and cancer.Key words: epidermis, lineage differentiation, embryonic stem cells.

scholarly journals The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 453
Author(s):  
Susana M. Chuva de Sousa Lopes ◽  
Marta S. Alexdottir ◽  
Gudrun Valdimarsdottir
Keyword(s):  
Stem Cell ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cell Model ◽  
Embryonic Stem ◽  
Model Systems ◽  
Special Focus ◽  
Placental Development

Emerging data suggest that a trophoblast stem cell (TSC) population exists in the early human placenta. However, in vitro stem cell culture models are still in development and it remains under debate how well they reflect primary trophoblast (TB) cells. The absence of robust protocols to generate TSCs from humans has resulted in limited knowledge of the molecular mechanisms that regulate human placental development and TB lineage specification when compared to other human embryonic stem cells (hESCs). As placentation in mouse and human differ considerably, it is only with the development of human-based disease models using TSCs that we will be able to understand the various diseases caused by abnormal placentation in humans, such as preeclampsia. In this review, we summarize the knowledge on normal human placental development, the placental disease preeclampsia, and current stem cell model systems used to mimic TB differentiation. A special focus is given to the transforming growth factor-beta (TGFβ) family as it has been shown that the TGFβ family has an important role in human placental development and disease.

scholarly journals In vitro Studies on PGC or PGC-Like Cells in Cultured Yolk Sac Cells and Embryonic Stem Cells of the Mouse.

2000 ◽  
Vol 63 (3) ◽  
pp. 229-241 ◽  
Author(s):  
Shin-ichiro NAKAGAWA ◽  
Sakura SABURI ◽  
Keitaro YAMANOUCHI ◽  
Hideaki TOJO ◽  
Chikashi TACHI
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Yolk Sac ◽  
In Vitro Studies ◽  
Yolk Sac Cells

scholarly journals Interaction of retinoic acid and scl controls primitive blood development

Blood ◽  
2010 ◽  
Vol 116 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Jill L. O. de Jong ◽  
Alan J. Davidson ◽  
Yuan Wang ◽  
James Palis ◽  
Praise Opara ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retinoic Acid ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Yolk Sac ◽  
Erythroid Progenitors ◽  
Self Renewal ◽  
Hematopoietic Development ◽  
Blood Island ◽  
Primitive Hematopoiesis

Abstract Hematopoietic development during embryogenesis involves the interaction of extrinsic signaling pathways coupled to an intrinsic cell fate that is regulated by cell-specific transcription factors. Retinoic acid (RA) has been linked to stem cell self-renewal in adults and also participates in yolk sac blood island formation. Here, we demonstrate that RA decreases gata1 expression and blocks primitive hematopoiesis in zebrafish (Danio rerio) embryos, while increasing expression of the vascular marker, fli1. Treatment with an inhibitor of RA biosynthesis or a retinoic acid receptor antagonist increases gata1+ erythroid progenitors in the posterior mesoderm of wild-type embryos and anemic cdx4−/− mutants, indicating a link between the cdx-hox signaling pathway and RA. Overexpression of scl, a DNA binding protein necessary for hematopoietic development, rescues the block of hematopoiesis induced by RA. We show that these effects of RA and RA pathway inhibitors are conserved during primitive hematopoiesis in murine yolk sac explant cultures and embryonic stem cell assays. Taken together, these data indicate that RA inhibits the commitment of mesodermal cells to hematopoietic fates, functioning downstream of cdx4 and upstream of scl. Our studies establish a new connection between RA and scl during development that may participate in stem cell self-renewal and hematopoietic differentiation.

scholarly journals Cell-autonomous differentiation of human primed embryonic stem cells into trophoblastic syncytia through the nascent amnion-like cell state

2021 ◽  
Author(s):  
Masatoshi Ohgushi ◽  
Mototsugu Eiraku
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Embryo ◽  
Embryonic Stem ◽  
Cell State ◽  
Transient Population ◽  
Post Implantation

Human primed embryonic stem cells (pESCs) are known to be converted to cells with several trophoblast properties, but it has remained controversial whether this phenomenon represents the inherent differentiation competence of human pESCs to trophoblast lineages. In this study, we report that chemical blockage of ACTIVIN/NODAL and FGF signals is sufficient to steer human pESCs into GATA3-expressing cells that give rise to hormone-producing syncytia analogous to syncytiotrophoblasts of the post-implantation stage of the human embryo. Taking advantage of this system, we identified two distinct modes of cell-autonomous genetic programs and their coordinated actions to initiate the differentiation. We also found a transient population reminiscent of nascent amnion and then a spontaneous branch of differentiation trajectory leading to syncytiotrophoblast-like syncytial cells. These results provide insights into the possible extraembryonic differentiation pathway that is unique in primate embryogenesis and is relevant to the trophoblast competence of human primed pluripotent stem cells.

scholarly journals daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009881
Author(s):  
Matthew J. Wirick ◽  
Allison R. Cale ◽  
Isaac T. Smith ◽  
Amelia F. Alessi ◽  
Margaret R. Starostik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Rna Binding ◽  
Cell Model ◽  
Cell Types ◽  
Adult Cell ◽  
Heterochronic Gene ◽  
Foxo Transcription Factors ◽  
Dauer Larvae

Many tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote quiescence and stem cell maintenance, but the mechanisms by which FOXO proteins promote multipotency during quiescence are still emerging. The single FOXO ortholog in C. elegans, daf-16, promotes entry into a quiescent and stress-resistant larval stage called dauer in response to adverse environmental cues. During dauer, stem and progenitor cells maintain or re-establish multipotency to allow normal development to resume after dauer. We find that during dauer, daf-16/FOXO prevents epidermal stem cells (seam cells) from prematurely adopting differentiated, adult characteristics. In particular, dauer larvae that lack daf-16 misexpress collagens that are normally adult-enriched. Using col-19p::gfp as an adult cell fate marker, we find that all major daf-16 isoforms contribute to opposing col-19p::gfp expression during dauer. By contrast, daf-16(0) larvae that undergo non-dauer development do not misexpress col-19p::gfp. Adult cell fate and the timing of col-19p::gfp expression are regulated by the heterochronic gene network, including lin-41 and lin-29. lin-41 encodes an RNA-binding protein orthologous to LIN41/TRIM71 in mammals, and lin-29 encodes a conserved zinc finger transcription factor. In non-dauer development, lin-41 opposes adult cell fate by inhibiting the translation of lin-29, which directly activates col-19 transcription and promotes adult cell fate. We find that during dauer, lin-41 blocks col-19p::gfp expression, but surprisingly, lin-29 is not required in this context. Additionally, daf-16 promotes the expression of lin-41 in dauer larvae. The col-19p::gfp misexpression phenotype observed in dauer larvae with reduced daf-16 requires the downregulation of lin-41, but does not require lin-29. Taken together, this work demonstrates a novel role for daf-16/FOXO as a heterochronic gene that promotes expression of lin-41/TRIM71 to contribute to multipotent cell fate in a quiescent stem cell model.

daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71

2021 ◽  
Author(s):  
Matthew J Wirick ◽  
Allison R Cale ◽  
Isaac T Smith ◽  
Amelia F Alessi ◽  
Margaret R Starostik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Rna Binding ◽  
Cell Model ◽  
Cell Types ◽  
Adult Cell ◽  
Heterochronic Gene ◽  
Foxo Transcription Factors ◽  
Dauer Larvae

Many tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote quiescence and stem cell maintenance, but the mechanisms by which FOXO proteins promote multipotency during quiescence are still emerging. The single FOXO ortholog in C. elegans, daf-16, promotes entry into a quiescent and stress-resistant larval stage called dauer in response to adverse environmental cues. During dauer, stem and progenitor cells maintain or re-establish multipotency to allow normal development to resume after dauer. We find that during dauer, daf-16/FOXO prevents epidermal stem cells (seam cells) from prematurely adopting differentiated, adult characteristics. In particular, dauer larvae that lack daf-16 misexpress collagens that are normally adult-enriched. Using col-19p::gfp as an adult cell fate marker, we find that all major daf-16 isoforms contribute to opposing col-19p::gfp expression during dauer. By contrast, daf-16(0) larvae that undergo non-dauer development do not misexpress col-19p::gfp. Adult cell fate and the timing of col-19p::gfp expression are regulated by the heterochronic gene network, including lin-41 and lin-29. lin-41 encodes an RNA-binding protein orthologous to LIN41/TRIM71 in mammals, and lin-29 encodes a conserved zinc finger transcription factor. In non-dauer development lin-41 opposes adult cell fate by inhibiting the translation of lin-29, which directly activates col-19 transcription and promotes adult cell fate. We find that during dauer, lin-41 blocks col-19p::gfp expression, but surprisingly, lin-29 is not required in this context. Additionally, daf-16 promotes the expression of lin-41 in dauer larvae. The col-19p::gfp misexpression phenotype observed in dauer larvae with reduced daf-16 requires the downregulation of lin-41, but does not require lin-29. Taken together, this work demonstrates a novel role for daf-16/FOXO as a heterochronic gene that promotes expression of lin-41/TRIM71 to contribute to multipotent cell fate in a quiescent stem cell model.

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