Evidence map›Paper›PMID 26293300›Full record

ArticleDevelopment (Cambridge, England)2015

Defining the three cell lineages of the human blastocyst by single-cell RNA-seq.

Paul Blakeley, Norah M E Fogarty, Ignacio del Valle, Sissy E Wamaitha, Tim Xiaoming Hu, Kay Elder, Philip Snell, Leila Christie, Paul Robson, Kathy K Niakan

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 218 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
218citing papers in PubMed, 1 pooled it
24.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

218 citing papers in PubMed, 1 synthesis or guideline pooled it, 491 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. The RNA mThe EMBO journal · 2025
    Article
  18. Article
  19. Article
  20. Article

158 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Paul BlakeleyHuman Embryology and Stem Cell Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
Norah M E FogartyHuman Embryology and Stem Cell Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
Ignacio del ValleHuman Embryology and Stem Cell Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
Sissy E WamaithaHuman Embryology and Stem Cell Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
Tim Xiaoming HuGenome Institute of Singapore, A-STAR, Singapore 138672, Singapore MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
Kay ElderBourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK.
Philip SnellBourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK.
Leila ChristieBourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK.
Paul RobsonGenome Institute of Singapore, A-STAR, Singapore 138672, Singapore The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
Kathy K NiakanHuman Embryology and Stem Cell Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK kathy.niakan@crick.ac.uk.
The Francis Crick Institute · GBBourn Hall Clinic · GBAgency for Science, Technology and Research · SGJackson Laboratory · US

Funding

Cancer Research UKMedical Research Council MC_UP_1202/9Wellcome Trust
6 · The paper itself

Abstract

Here, we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast, including the transcription factor KLF17. Key components of the TGF-β signalling pathway, including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1, are also enriched in the human epiblast. Intriguingly, inhibition of TGF-β signalling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although the key trophectoderm factors Id2, Elf5 and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics, including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparison of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared with mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells.

Indexed as

AnimalsBlastocystCell LineageGene Expression ProfilingGene Expression Regulation, DevelopmentalHumansMicePrincipal Component AnalysisSequence Analysis, RNASingle-Cell AnalysisSpecies SpecificityEmbryonic stem cellsEpiblastHumanMouseRNA-sequencingTrophectoderm

Identifiers

PMID26293300
PMCPMC4582176
OpenAlexW2125336256

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.