Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification

Dattani, Anish; Corujo-Simon, Elena; Radley, Arthur; Heydari, Tiam; Taheriabkenar, Yasaman; Carlisle, Francesca; Lin, Simeng; Liddle, Corin; Mill, Jonathan; Zandstra, Peter W.; Nichols, Jennifer; Guo, Ge

doi:10.1016/j.stem.2024.05.003

Cited by 10 publications

(1 citation statement)

References 59 publications

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“…These findings illustrate how ES and our UMAP embedding can be used to identify new gene expression patterns that may aid future experiments and analyses, also exemplified in Dattani et al (2024) .…”

Section: Resultsmentioning

confidence: 67%

Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting

Radley,

Boeing,

Smith

2024

Development

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Analysis of single cell transcriptomics (scRNA-seq) data is typically performed after sub-setting to highly variable genes (HVGs). Here we show that Entropy Sorting provides an alternative mathematical framework for feature selection. On synthetic datasets, continuous entropy sort feature weighting (cESFW) outperforms HVG selection in distinguishing cell state specific genes. We apply cESFW to six merged scRNA-seq datasets spanning human early embryo development. Without smoothing or augmenting the raw counts matrices, cESFW generates a high-resolution embedding displaying coherent developmental progression from 8-cell to post-implantation stages and delineating 15 distinct cell states. The embedding highlights sequential lineage decisions during blastocyst development while unsupervised clustering identifies branch point populations obscured in previous analyses. The first branching region, where morula cells become specified for inner cell mass or trophectoderm, includes cells previously asserted to lack a developmental trajectory. We quantify the relatedness of different pluripotent stem cell cultures to distinct embryo cell types and identify marker genes of naïve and primed pluripotency. Finally, by revealing genes with dynamic lineage-specific expression we provide markers for staging progression from morula to blastocyst.

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Section: Resultsmentioning

confidence: 67%

Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting

Radley,

Boeing,

Smith

2024

Development

Self Cite

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A brief chronicle of research on human pluripotent stem cells

Pera

2024

BioEssays

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

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Propagating pluripotency – The conundrum of self‐renewal

Smith

2024

BioEssays

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

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Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification

Cited by 10 publications

References 59 publications

Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting

Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting

A brief chronicle of research on human pluripotent stem cells

Propagating pluripotency – The conundrum of self‐renewal

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