Primate gastrulation and early organogenesis at single-cell resolution

Abstract

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8–11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species—for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation—and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.

Zebrahub – Multimodal Zebrafish Developmental Atlas Reveals the State-Transition Dynamics of Late-Vertebrate Pluripotent Axial Progenitors

“…4i). This analysis confirmed that during early stages (10, 12, and 14 hpf), NMP velocities point towards both mesoderm and neural tissue, whereas during later stages (16,19, and 24 hpf), they primarily point towards the mesoderm.…”

“…To gain a better understanding of the temporal dynamics of NMPs during early development, we re-analyzed the RNA velocity data at individual time points (10,12,14,16,19, and 24 hpf). At 10 hpf (the end of gastrulation, beginning of axial extension -Fig.…”

“…Advances in fluorescence light-sheet microscopy have enabled in-toto imaging of embryonic development at cellular resolution using zebrafish, mice, and drosophila, allowing for the reconstruction of specific lineages based on cell positions over time [6][7][8][9][10] . Single-cell RNA sequencing (scRNAseq) technologies have provided complementary means of tracking cell lineages based on their transcriptomes over developmental time [11][12][13][14][15][16][17][18][19][20] . Here, we combine light-sheet microscopy with scRNAseq of individual developing zebrafish embryos to construct a comprehensive multimodal atlas of cell lineages and molecular states at unique spatiotemporal resolution.…”

Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation

“…Near identical cell populations can be found by analysis of existing mouse (E8.0-E8.5) 32 and macaque (CS9-CS11) 33 single-cell transcriptomic data highlighting the remarkable conservation of trunk formation across vertebrates ( Figure S3a-c ). However, the number of notochord cells in mouse were much lower than in chick and very few progenitors were captured, perhaps due to the small notochord size in mouse.…”

The gut microbiome modulates the transformation of microglial subtypes

“…We followed the "Reduce, Reuse, Recycle" waste hierarchy, using the minimum sample size of 3 samples/group (n = 3/GF, n = 3/SPF, n = 3/CGF). This sample size is also commonly used in the single-cell analysis of murine brain tissues in previous studies [22,28,29,[34][35][36][37].…”