Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid

Sözen, Berna; Cox, Andy; Jonghe, Joachim De; Bao, Min; Hollfelder, Florian; Glover, David M.; Zernicka‐Goetz, Magdalena

doi:10.1016/j.devcel.2019.11.014

Cited by 184 publications

(187 citation statements)

References 62 publications

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“…Although not abundant, the presence of TE or ExE-like cells in B-blastoids is intriguing and leaves the door open for the possibility that some EPSCs may indeed harbor potential to differentiate into trophoblast. Of note, ESCs are also able, in some cases, to form blastoids 44,36 but whether they also recapitulate the gene regulatory programs of natural embryos like EPSC-derived blastoids do remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…The ultimate proof of totipotency is the ability of a single cell type, or more stringently a single cell, to give rise to an entire blastocyst and subsequently a viable and fertile animal. Recently, blastocyst-like structures, termed blastoids, have been generated in vitro from different stem cell types 43,44,35,36 . These protocols use different combinations of growth factors and inhibitors to generate blastoids, which in multiple aspects resemble real blastocyst stage embryos, although until now none have been able to generate viable animals.…”

Section: In Vitro Blastoid-forming Ability Of D-epscs Based On LI Etmentioning

confidence: 99%

“…These protocols use different combinations of growth factors and inhibitors to generate blastoids, which in multiple aspects resemble real blastocyst stage embryos, although until now none have been able to generate viable animals. Most notably, two recent reports used D-EPSCs, either as a sole stem cell source (Belmonte group, B-blastoid) 35 or in combination with TSCs (Zernicka-Goetz group, ZG-blastoid) 36 to generate blastoids. Importantly, a large proportion of the blastoid cells generated with only D-EPSCs showed expression of genes previously associated with post-implantation stage lineages and not cells of the blastocyst.…”

Section: In Vitro Blastoid-forming Ability Of D-epscs Based On LI Etmentioning

confidence: 99%

“…Both cell types showed molecular and functional features that suggested expanded pluripotency, such as totipotency-associated marker gene expression and contribution to the EPI, PE as well as TE lineages using chimeric assays. Additionally, recent studies reported the ability of EPSCs, alone or in combination with TSCs, to self-assemble into blastocyst-like structures, termed blastoids, that contain cells with features of all three embryonic lineages 35,36 . These studies suggested that stem cells with the potential to give rise to both ICM and TE lineages, properties that define totipotent stem cells, can be isolated and expanded in vitro.…”

Section: Introductionmentioning

confidence: 99%

“…Supporting this notion, D-EPSCs were not able to give rise to a TE-like layer under a different blastoid forming protocol (ZG-blastoid). Instead, TSCs had to be used 36 . It should however still be considered that the TE or ExE-like blastoid cells fail to express Cdx2, Gata3 and Elf5 transcripts in similar levels to endogenous TE or ExE of the embryo suggesting that their transcriptional profile still is distinct from in vivo cells.…”

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confidence: 99%

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Defining totipotency using criteria of increasing stringency

Pósfai

Janiszewski

et al. 2020

Preprint

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Totipotency is the ability of a single cell to give rise to all the differentiated cells that build the conceptus, yet how to capture this property in vitro remains incompletely understood. Defining totipotency relies upon a variety of assays of variable stringency. Here we describe criteria to define totipotency. We illustrate how distinct criteria of increasing stringency can be used to judge totipotency by evaluating candidate totipotent cell types in the mouse, including early blastomeres and expanded or extended pluripotent stem cells. Our data challenge the notion that expanded or extended pluripotent states harbor increased totipotent potential relative to conventional embryonic stem cells under in vivo conditions.

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Section: Discussionmentioning

confidence: 99%

Section: In Vitro Blastoid-forming Ability Of D-epscs Based On LI Etmentioning

confidence: 99%

Section: In Vitro Blastoid-forming Ability Of D-epscs Based On LI Etmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Defining totipotency using criteria of increasing stringency

Pósfai

Janiszewski

et al. 2020

Preprint

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From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell‐based Embryo Models along the Embryonic Timeline

et al. 2021

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In recent years, stem cell-based models that reconstruct mouse and human embryogenesis have gained significant traction due to their near-physiological similarity to natural embryos. Embryo models can be generated in large numbers, provide accessibility to a variety of experimental tools such as genetic and chemical manipulation, and confer compatibility with automated readouts, which permits exciting experimental avenues for exploring the genetic and molecular principles of self-organization, development, and disease. However, the current embryo models recapitulate only snapshots within the continuum of embryonic development, allowing the progression of the embryonic tissues along a specific direction. Hence, to fully exploit the potential of stem cell-based embryo models, multiple important gaps in the developmental landscape need to be covered. These include recapitulating the lesser-explored interactions between embryonic and extraembryonic tissues such as the yolk sac, placenta, and the umbilical cord; spatial and temporal organization of tissues; and the anterior patterning of embryonic development. Here, it is detailed how combinations of stem cells and versatile bioengineering technologies can help in addressing these gaps and thereby extend the implications of embryo models in the fields of cell biology, development, and regenerative medicine.

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Podocalyxin‐Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway

et al. 2022

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Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts. The addition of exogenous cholesterol fully restores PODXL knockdown-mediated loss of pluripotency. PODXL affects lipid raft dynamics via the regulation of cholesterol. PODXL recruits the RAC1/CDC42/actin network to regulate SREBP1 and SREBP2 maturation and lipid raft dynamics. Single-cell RNA sequencing reveals PODXL overexpression enhanced chimerism between human cells in mouse host embryos (hEPSCs 57%). Interestingly, in the human-mouse chimeras, laminin and collagen signaling-related pathways are dominant in PODXL overexpressing cells. It is concluded that cholesterol regulation via PODXL signaling is critical for ESC/EPSC.

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Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid

Cited by 184 publications

References 62 publications

Defining totipotency using criteria of increasing stringency

Defining totipotency using criteria of increasing stringency

From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell‐based Embryo Models along the Embryonic Timeline

Podocalyxin‐Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway

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