Establishment of bovine extraembryonic endoderm cells DOI Creative Commons
Hao Ming,

Giovanna Scatolin,

Alejandro Ojeda

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Understanding the mechanisms of hypoblast development and its role in implantation is critical for improving farm animal reproduction, but it hampered by lack research models. Here we report that a chemical cocktail (FGF4, BMP4, IL-6, XAV939, A83-01) enables de novo derivation long-term culture bovine extraembryonic endoderm cells (bXENs). Transcriptomic epigenomic analyses confirmed identity bXENs revealed they are resemble lineages early peri-implantation embryos. We showed help maintain stemness ESCs prevent them from differentiation. In presence signaling sustaining bXENs, growth progression epiblasts also facilitated developing pre-implantation embryo. Furthermore, through 3D assembly with TSCs, developed an improved blastocyst like structure (bovine blastoid) resembles blastocyst. The XENs blastoids established this study represent accessible vitro models understanding reproductive efficiency livestock species.

Language: Английский

Tracking and mitigating imprint erasure during induction of naive human pluripotency at single-cell resolution DOI Creative Commons
Laura A. Fischer,

Brittany Meyer,

Mónica De los Reyes

et al.

Stem Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102419 - 102419

Published: Feb. 1, 2025

Highlights•A biallelic, dual-colored fluorescent reporter at the imprinted SNRPN locus in hPSCs•Biallelic expression is rapidly induced during primed-to-naive resetting•Acquisition of biallelic irreversible upon re-priming•ZFP57 overexpression mitigates imprint erasure resettingSummaryNaive human pluripotent stem cells (hPSCs) model pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded naive hPSCs, which represents an important deviation from epiblast vivo. To track dynamics resetting real time, we established a both alleles locus. During resetting, becomes most cells, and re-priming. We utilized this live-cell to evaluate chemical genetic strategies minimize erasure. Decreasing level MEK/ERK inhibition or overexpressing KRAB zinc-finger protein ZFP57 protected subset imprints resetting. Combining these two levels further extent than either strategy alone. This study offers experimental tool enhance stability transitions between states vitro.Graphical abstract

Language: Английский

Citations

1
Pluripotent cell states and fates in human embryo models DOI
Berna Sözen, Patrick Tam, Martín F. Pera

et al.

Development, Journal Year: 2025, Volume and Issue: 152(7)

Published: April 1, 2025

ABSTRACT Pluripotency, the capacity to generate all cells of body, is a defining property transient population epiblast found in pre-, peri- and post-implantation mammalian embryos. As development progresses, undergo dynamic transitions pluripotency states, concurrent with specification extra-embryonic embryonic lineages. Recently, stem cell-based models pre- human have been developed using that capture key properties at different developmental stages. Here, we review early primate development, comparing states vivo cultured pluripotent representative these states. We consider how status starting influences embryo and, turn, what can learn about epiblast. Finally, discuss limitations questions arising from pioneering studies this emerging field.

Language: Английский

Citations

1
Early human development and stem cell-based human embryo models DOI Creative Commons
Marta N. Shahbazi, Vincent Pasque

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(10), P. 1398 - 1418

Published: Oct. 1, 2024

Language: Английский

Citations

5
Propagating pluripotency – The conundrum of self‐renewal DOI Creative Commons
Austin Smith

BioEssays, Journal Year: 2024, Volume and Issue: 46(12)

Published: Aug. 23, 2024

Abstract The discovery of mouse embryonic stem cells in 1981 transformed research mammalian developmental biology and functional genomics. subsequent generation human pluripotent (PSCs) the development molecular reprogramming have opened unheralded avenues for drug cell replacement therapy. Here, I review history PSCs from perspective that long‐term self‐renewal is a product vitro signaling environment, rather than an intrinsic feature embryos. discuss relationship between states captured to stages epiblast embryo suggest key considerations evaluation PSCs. A remaining fundamental challenge determine whether naïve pluripotency can be propagated broad range mammals by exploiting common principles gene regulatory architecture.

Language: Английский

Citations

4
Divergent destinies: insights into the molecular mechanisms underlying EPI and PE fate determination DOI Creative Commons
Paraskevi Athanasouli, Tijs Vanhessche, Frederic Lluı́s

et al.

Life Science Alliance, Journal Year: 2025, Volume and Issue: 8(3), P. e202403091 - e202403091

Published: Jan. 8, 2025

Mammalian pre-implantation development is entirely devoted to the specification of extra-embryonic lineages, which are fundamental for embryo morphogenesis and support. The second fate decision taken just before implantation, as defined by epiblast (EPI) primitive endoderm (PE) specification. Later, EPI forms proper PE contributes formation yolk sac. molecularly morphologically distinct lineages final step a multistage process, begins when bipotent progenitor cells diverge into separate fates. Despite advances in uncovering molecular mechanisms underlying differential transcriptional patterns that dictate how apparently identical make decisions lineage integrity maintained, detailed overview these still lacking. In this review, we dissect process four stages (initiation, specification, segregation, maintenance) provide comprehensive understanding involved establishment mouse. addition, discuss conservation key processes humans, based on most recent findings.

Language: Английский

Citations

0
Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee DOI Creative Commons
Tao Huang, Arthur Radley, Ayaka Yanagida

et al.

Cell stem cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ self-renewal requirements extraembryonic lineage potency. Here, we investigated generation chimpanzee PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that is enabled inhibition Polycomb repressive complex 2 (PRC2). Expanded show global transcriptome proximity embryo pre-implantation epiblast, with shared expression a subset pluripotency transcription factors. Chimpanzee can transition multilineage competence differentiate into trophectoderm hypoblast, forming tri-lineage blastoids. They thus provide higher primate comparative model for studying embryogenesis. Genetic deletions confirm PRC2 mediates growth arrest. Further, overcomes roadblock feeder-free propagation Therefore, excess deposition chromatin modification H3K27me3 an unexpected barrier PSC self-renewal.

Language: Английский

Citations

0
The guinea pig serves as an alternative model to study human preimplantation development DOI Creative Commons
Jésica Canizo, Cheng Zhao, Sophie Petropoulos

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Abstract Preimplantation development is an important window of human embryogenesis. However, ethical constraints and the limitations involved in studying embryos often necessitate use alternative model systems. Here we identify guinea pig as a promising small animal to study preimplantation development. Using single-cell RNA-sequencing, generated atlas development, revealing its close resemblance early embryogenesis terms timing compaction, early-, mid- late-blastocyst formation, implantation, spatio-temporal expression key lineage markers. We also show conserved roles Hippo, MEK-ERK JAK-STAT signalling. Furthermore, multi-species analysis highlights divergent genes during pluripotency. The serves valuable for advancing stem cell research, can be leveraged better understand longer-term impact exposures on offspring outcomes.

Language: Английский

Citations

0
Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting DOI Creative Commons
Arthur Radley, Stefan Boeing, Austin Smith

et al.

Development, Journal Year: 2024, Volume and Issue: 151(11)

Published: May 1, 2024

Analysis of single cell transcriptomics (scRNA-seq) data is typically performed after subsetting to highly variable genes (HVGs). Here, we show that Entropy Sorting provides an alternative mathematical framework for feature selection. On synthetic datasets, continuous Sort Feature Weighting (cESFW) outperforms HVG selection in distinguishing cell-state-specific genes. We apply cESFW six merged scRNA-seq datasets spanning human early embryo development. Without smoothing or augmenting the raw counts matrices, generates a high-resolution embedding displaying coherent developmental progression from eight-cell post-implantation stages and delineating 15 distinct states. The highlights sequential lineage decisions during blastocyst development, while unsupervised clustering identifies branch point populations obscured previous analyses. first branching region, where morula cells become specified inner mass trophectoderm, includes previously asserted lack trajectory. quantify relatedness different pluripotent stem cultures types identify marker naïve primed pluripotency. Finally, by revealing with dynamic lineage-specific expression, provide markers staging blastocyst.

Language: Английский

Citations

3
A brief chronicle of research on human pluripotent stem cells DOI
Martín F. Pera

BioEssays, Journal Year: 2024, Volume and Issue: 46(12)

Published: July 26, 2024

Today, human pluripotent stem cell technologies find widespread application across biomedical research, as models for early development, platforms functional genomics, tools the study of disease, drug screening and toxicology, a renewable source cellular therapeutics range intractable diseases. The foundations this revolution rest on advances in wide disciplines, including cancer biology, assisted reproduction, culture organoid technology, somatic nuclear transfer, primate embryology, single-cell gene editing. This review surveys slow emergence pluripotency exponential growth field during past several decades.

Language: Английский

Citations

3
Unraveling the function of FGF signaling in human hypoblast specialization DOI
Hao Wu, Jinglei Zhai, Hongmei Wang

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(7), P. 945 - 946

Published: July 1, 2024

Language: Английский

Citations

1