Defining the three cell lineages of the human blastocyst by single-cell RNA-seq
-
- Paul Blakeley
- The Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK
-
- Norah M.E. Fogarty
- The Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK
-
- Ignacio del Valle
- The Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK
-
- Sissy E. Wamaitha
- The Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK
-
- Tim Xiaoming Hu
- Genome Institute of Singapore, A-STAR, 138672, Singapore
-
- Kay Elder
- Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK
-
- Philip Snell
- Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK
-
- Leila Christie
- Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK
-
- Paul Robson
- Genome Institute of Singapore, A-STAR, 138672, Singapore
-
- Kathy K. Niakan
- The Francis Crick Institute, Mill Hill Laboratory, London, NW7 1AA, UK
Description
<jats:p>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 signaling pathway including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1 are also enriched in the human epiblast. Intriguingly, inhibition of TGF-β signaling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although 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. Comparisons 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 to mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells.</jats:p>
Journal
-
- Development
-
Development 142 3151-, 2015-01-01
The Company of Biologists
- Tweet
Details 詳細情報について
-
- CRID
- 1363107370063799040
-
- ISSN
- 14779129
- 09501991
-
- Data Source
-
- Crossref