Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing
Open accessAbstract
Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Humans and mice share core transcriptional programmes in early development, but diverge at a later stage.
“This suggests that humans and mice share core transcriptional programmes in early development, but diverge at a later stage [12].”
From Gene co-expression analysis for functional classification and gene–disease predictions (2017) · cites this paper as [12]
The paper’s Abstract says human and mouse embryos share many core transcriptional programs, supporting the first part of the claim. It describes divergence in stage-specificity and timing, not divergence arising at a later stage; it says the species re-converge at the 8-cell-to-morula transition. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLarge-scale single-cell sequencing technology is increasingly used and the first co-expression studies using such techniques have uncovered cell-type-specific co-expression modules that would have gone undetected in multi-cell-type co-expression analyses.
“Large-scale single-cell sequencing technology is increasingly used and the first co-expression studies using such techniques have uncovered cell-type-specific co-expression modules that would have gone undetected in multi-cell-type co-expression analyses [5, 12].”
From Gene co-expression analysis for functional classification and gene–disease predictions (2017) · cites this paper as [12]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredPTBP1 is an RNA-binding protein that maintains non-neuronal splicing programs.
“PTBP1 is an RNA-binding protein that maintains non-neuronal splicing programs; its downregulation is a hallmark of neuronal differentiation during development.”
From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [12]
The supplied passages discuss gene-expression networks in early embryos, not PTBP1 or its role in splicing. Searches for PTBP1 and for polypyrimidine-tract binding protein in connection with neuronal splicing returned no passage addressing the claim; the copy therefore neither supports nor contradicts it. (LLM, conf=0.76)
Experimental — accuracy not yet measuredPTBP1 downregulation is a hallmark of neuronal differentiation during development.
“PTBP1 is an RNA-binding protein that maintains non-neuronal splicing programs; its downregulation is a hallmark of neuronal differentiation during development.”
From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [12]
The paper’s Abstract (page unavailable) describes gene-expression changes from oocyte to morula in human and mouse pre-implantation embryos, not neuronal differentiation. Searches for PTBP1, non-neuronal splicing, and neuronal differentiation found no passage in our copy addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredProtocols that lyse entire cells measure total mRNA, and consequently they mix the fluctuating nuclear RNA and the more stable cytoplasmic RNA and combine transcriptional and post-transcriptional effects in a single measurement.
“Second, protocols that lyse entire cells measure total mRNA, and consequently they mix the fluctuating nuclear RNA and the more stable cytoplasmic RNA177,178 and combine transcriptional and post-transcriptional effects in a single measurement.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [177]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 39 · Cited by 963
- Authors
- Xue, Z., Huang, K., Cai, C., Cai, L., Jiang, C.-Y., Feng, Y., Liu, Z., Zeng, Q., Cheng, L., Sun, Y. E., Liu, J.-Y., Horvath, S., & Fan, G.
- Affiliations
- Tongji University (CN)
- University of California, Los Angeles (US)
- Jiangsu Province Hospital (CN)
- Corresponding author
- Xue, Zhigang
- Fan, Guoping
- Venue
- Nature
- Published
- 2013-07-28
- Volume
- 500
- Issue
- 7464
- Pages
- 593-597
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4950944
- OpenAlex
- W2086277161
- Cited by
- 963
- References
- 39
- Citations by year
- 2026: 30 · 2025: 46 · 2024: 74 · 2023: 66 · 2022: 81 · 2021: 80 · 2020: 97 · 2019: 81 · 2018: 80 · 2017: 82 · 2016: 101 · 2015: 74 · 2014: 62 · 2013: 7 · 2012: 1
- FWCI
- 83.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Institute on Drug Abuse (P50DA005010)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD006576, P30HD004612)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- preimplantation embryo development, human embryo, mouse embryo, oocyte transcriptome, monoallelic expression, single nucleotide polymorphisms, hub genes, gene co-expression network, transcriptome dynamics, morula, cross-species comparison, gene regulatory mechanisms
- MeSH terms
- Alleles, Animals, Blastocyst, Cell Cycle, Embryo, Mammalian, Humans, Morula, Oocytes, Sequence Analysis, RNA, Gene Expression Regulation, Developmental, Gene Expression Profiling, Embryonic Development, Mice, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
