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Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting.
Radley, Arthur; Boeing, Stefan; Smith, Austin.
Afiliação
  • Radley A; Living Systems Institute, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
  • Boeing S; Bioinformatics and Biostatistics Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UK.
  • Smith A; Living Systems Institute, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
Development ; 151(11)2024 Jun 01.
Article em En | MEDLINE | ID: mdl-38691188
ABSTRACT
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 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 eight-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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linhagem da Célula / Entropia / Desenvolvimento Embrionário / Embrião de Mamíferos / Análise de Célula Única / Transcriptoma Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linhagem da Célula / Entropia / Desenvolvimento Embrionário / Embrião de Mamíferos / Análise de Célula Única / Transcriptoma Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article