Committing the primordial germ cell: An updated molecular perspective

Tan, Haihan; Tee, Wee-Wei

doi:10.1002/wsbm.1436

Cited by 17 publications

(15 citation statements)

References 108 publications

(233 reference statements)

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“…We also identified Endoderm-1 which may represent precursors of primitive and definitive endoderm. However, there are known differences between mouse and human in the formation of ExE cells (Shahbazi and Zernicka-Goetz, 2018) and PGC (Tan and Tee, 2019). Accordingly, we did not find similarities between mouse PGC and Endoderm-2, a cluster enriched in NANOS3, TFAP2C, and other primate PGC and hPGCLC markers.…”

Section: Discussioncontrasting

confidence: 80%

“…Interestingly, however, the Endoderm-2 cluster matched primarily with mouse epiblast cells despite showing resemblance to ExE ectoderm and ExE endoderm ( Figure 3I). We reasoned that the mismatch occurred because the Endoderm-2 cluster primarily contained hPGCLC, whose formation and gene expression diverge from mouse PGCs (Tan and Tee, 2019). A parallel comparison of our gastruloid data with hPGCLCs derived using in vitro human amnion model (Zheng et al, 2019), corroborated a strong correlation in gene expression between Endoderm-2 and hPGCLCs in that study ( Figure S3H).…”

Section: Gastruloids Contain Cells Similar In Gene Expression Profilesupporting

confidence: 70%

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High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human embryonic stem cell gastruloid cultures

Fu²,

He³

et al. 2020

Preprint

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During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells with radial organization. Single-cell RNA sequencing and cross-species comparisons with mouse and cynomolgus monkey gastrulae suggest that gastruloids contain seven major cell types, including epiblast, ectoderm, mesoderm, endoderm, and extraembryonic trophoblast-and amnion-like cells. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic cells but mixed with mesodermal cells. Our work demonstrates that the gastruloid system supports primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.

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Section: Discussioncontrasting

confidence: 80%

Section: Gastruloids Contain Cells Similar In Gene Expression Profilesupporting

confidence: 70%

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human embryonic stem cell gastruloid cultures

Fu²,

He³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Interestingly however, cross-species comparison with mouse showed that the hPGCLC cluster had predicted labels of epiblast (64%), ExE ectoderm (13%), and ExE endoderm (10%; Figure 3I ). We reasoned the mismatch occurred because hPGCLC formation and gene expression diverge from mouse PGCs ( Tan and Tee, 2019 ). Accordingly, we found that the PGC module score, based on primate PGC predictors, of monkey PGCs was similar to that of gastruloid hPGCLCs but significantly higher than that of mouse PGCs (p<0.0001; Figure 5E ).…”

Section: Resultsmentioning

confidence: 99%

“…Nonetheless, we found similarities between epiblast cell types, gastrulating cells (E-Gast and L-Gast1/2) to mouse PS and mesoderm, VE/YE to mouse ExE Endoderm, and TE to mouse ExE Ectoderm, suggesting conservation in the formation of these cell types. However, monkey E-PGCs were primarily predicted to correspond to mouse epiblast, PS, and nascent mesoderm than PGC, reflecting species differences in PGC formation ( Tan and Tee, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures

Minn

et al. 2020

eLife

100

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During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.

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“…Stem cell treatment has been proposed as a potential intervention to improve endometrial quality and receptivity . However, the field is moving toward cell‐free therapies to improve safety and efficacy, making the function of endometrial‐derived EVs in improving embryo implantation potential described here an attractive future therapy to improve fertility and the success of IVF cycles in which implantation failure is a major limiting factor.…”

Section: Discussionmentioning

confidence: 99%

Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal‐Embryo Communication

et al. 2019

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Embryo implantation into maternal endometrium is critical for initiation and establishment of pregnancy, requiring developmental synchrony between endometrium and blastocyst. However, factors regulating human endometrial–embryo cross talk and facilitate implantation remain largely unknown. Extracellular vesicles (EVs) are emerging as important mediators of this process. Here, a trophectoderm spheroid‐based in vitro model mimicking the pre‐implantation human embryo is used to recapitulate important functional aspects of blastocyst implantation. Functionally, human endometrial EVs, derived from hormonally treated cells synchronous with implantation, are readily internalized by trophectoderm cells, regulating adhesive and invasive capacity of human trophectoderm spheroids. To gain molecular insights into mechanisms underpinning endometrial EV‐mediated enhancement of implantation, quantitative proteomics reveal critical alterations in trophectoderm cellular adhesion networks (cell adhesion molecule binding, cell–cell adhesion mediator activity, and cell adherens junctions) and metabolic and gene expression networks, and the soluble secretome from human trophectodermal spheroids. Importantly, transfer of endometrial EV cargo proteins to trophectoderm to mediate changes in trophectoderm function is demonstrated. This is highlighted by correlation among endometrial EVs, the trophectodermal proteome following EV uptake, and EV‐mediated trophectodermal cellular proteome, important for implantation. This work provides an understanding into molecular mechanisms of endometrial EV‐mediated regulation of human trophectoderm functions—fundamental in understanding human endometrium–embryo signaling during implantation.

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Committing the primordial germ cell: An updated molecular perspective

Cited by 17 publications

References 108 publications

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human embryonic stem cell gastruloid cultures

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human embryonic stem cell gastruloid cultures

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures

Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal‐Embryo Communication

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