Diverse Routes toward Early Somites in the Mouse Embryo

Guibentif, Carolina; Griffiths, J. B.; Imaz-Rosshandler, Iván; Ghazanfar, Shila; Nichols, Jennifer; Wilson, Valerie; Göttgens, Berthold; Marioni, John C.

doi:10.1016/j.devcel.2020.11.013

Cited by 55 publications

(74 citation statements)

References 85 publications

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“…Using pseudotime analysis, we identified two main developmental trajectories arising from the NMP cluster and leading to neural and mesodermal identities, supporting the bipotentiality of these cells ( Figure 3M , Figure 3—figure supplement 3E ). This is consistent with previous reports indicating that NMPs first form at E7.0 in mouse embryos ( Gouti et al, 2017 ; Guibentif et al, 2021 ), that is, at a roughly equivalent stage to chicken embryos ( Figure 1—figure supplement 1 ), which corresponds to the beginning of PS regression. Most NMP signature genes common to the three chicken NMP clusters were also expressed in the mouse NMP cluster ( Figure 3D, N , Figure 3—figure supplement 4 ).…”

Section: Resultssupporting

confidence: 93%

“…At stage 5HH, we identified a large cluster corresponding to epiblast cells, characterized by the expression of SALL4 or FRZB . Another cluster contained cells co-expressing markers of paraxial mesoderm ( MSGN1, MEOX1 ) and lateral plate ( TWIST1, GATA5 ), suggesting that they correspond to ingressed mesoderm contributing to the anterior-most somites as recently shown in mouse embryos ( Guibentif et al, 2021 ). A cluster containing early neural plate cells characterized by expression of SFRP2 and PDGFA , as well as small clusters corresponding to the endoderm ( SOX17, FOXA2 ) and the notochord ( CHRD, NOTO ), was also identified.…”

Section: Resultssupporting

confidence: 53%

“…We found 44 conserved genes between the two species showing a striking enrichment in Wnt pathway genes including known targets such as Axin2, T, and Fgf8 as well as pathway members including Wnt3a/5a/5b/8a and Wls . We next compared the signature genes for the chicken NMP population identified in this study with NMP signatures identified in mouse embryos ( Dias et al, 2020 ; Diaz-Cuadros et al, 2020 ; Gouti et al, 2017 ; Guibentif et al, 2021 ) as well as in human SOX2/T-positive cells differentiated in vitro ( Diaz-Cuadros et al, 2020 ; Supplementary file 5 ). We identified 38 genes conserved in four or five of the six datasets.…”

Section: Resultsmentioning

confidence: 99%

“… We used the list of differentially expressed genes (DEGs) identified in Dias et al, 2020 , Guibentif et al, 2021 ; Gouti et al, 2017 ; the top 350 genes of Table 5 from Guibentif et al, 2021 . For the human gene list, we computed the list of DEG in the NMP cluster compared to the pluripotent stem cell cluster and took the 350 top genes from the Diaz-Cuadros et al, 2020 study.…”

Section: Additional Filesmentioning

confidence: 99%

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Dynamics of primitive streak regression controls the fate of neuromesodermal progenitors in the chicken embryo

Guillot

Djeffal

Michaut

et al. 2021

eLife

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In classical descriptions of vertebrate development, the segregation of the three embryonic germ layers completes by the end of gastrulation. Body formation then proceeds in a head to tail fashion by progressive deposition of lineage-committed progenitors during regression of the primitive streak (PS) and tail bud (TB). The identification by retrospective clonal analysis of a population of neuromesodermal progenitors (NMPs) contributing to both musculoskeletal precursors (paraxial mesoderm) and spinal cord during axis formation challenged these notions. However, classical fate mapping studies of the PS region in amniotes have so far failed to provide direct evidence for such bipotential cells at the single-cell level. Here, using lineage tracing and single-cell RNA sequencing in the chicken embryo, we identify a resident cell population of the anterior PS epiblast, which contributes to neural and mesodermal lineages in trunk and tail. These cells initially behave as monopotent progenitors as classically described and only acquire a bipotential fate later, in more posterior regions. We show that NMPs exhibit a conserved transcriptomic signature during axis elongation but lose their epithelial characteristicsin the TB. Posterior to anterior gradients of convergence speed and ingression along the PS lead to asymmetric exhaustion of PS mesodermal precursor territories. Through limited ingression and increased proliferation, NMPs are maintained and amplified as a cell population which constitute the main progenitors in the TB. Together, our studies provide a novel understanding of the PS and TB contribution through the NMPs to the formation of the body of amniote embryos.

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Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Additional Filesmentioning

confidence: 99%

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Dynamics of primitive streak regression controls the fate of neuromesodermal progenitors in the chicken embryo

Guillot

Djeffal

Michaut

et al. 2021

eLife

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“…The G1ER cell line represents an in vitro model, and the published differential gene expression data were from bulk microarray profiling, thus precluding any analysis of single-cell gene expression kinetics. We therefore turned to our recently reported Chimaera-Seq approach, whereby scRNA-Seq is coupled with mouse chimeric embryo technology, to define both cellular and molecular consequences of gene knockouts in vivo [ 25 , 31 ]. We used our standard embryonic stem cells (ESCs) expressing a constitutive tdTomato (tdTom) fluorescent marker gene to generate a Gata1 knockout line (see “ Methods ”).…”

Section: Resultsmentioning

confidence: 99%

Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation

et al. 2021

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Background Single-cell technologies are transforming biomedical research, including the recent demonstration that unspliced pre-mRNA present in single-cell RNA-Seq permits prediction of future expression states. Here we apply this RNA velocity concept to an extended timecourse dataset covering mouse gastrulation and early organogenesis. Results Intriguingly, RNA velocity correctly identifies epiblast cells as the starting point, but several trajectory predictions at later stages are inconsistent with both real-time ordering and existing knowledge. The most striking discrepancy concerns red blood cell maturation, with velocity-inferred trajectories opposing the true differentiation path. Investigating the underlying causes reveals a group of genes with a coordinated step-change in transcription, thus violating the assumptions behind current velocity analysis suites, which do not accommodate time-dependent changes in expression dynamics. Using scRNA-Seq analysis of chimeric mouse embryos lacking the major erythroid regulator Gata1, we show that genes with the step-changes in expression dynamics during erythroid differentiation fail to be upregulated in the mutant cells, thus underscoring the coordination of modulating transcription rate along a differentiation trajectory. In addition to the expected block in erythroid maturation, the Gata1-chimera dataset reveals induction of PU.1 and expansion of megakaryocyte progenitors. Finally, we show that erythropoiesis in human fetal liver is similarly characterized by a coordinated step-change in gene expression. Conclusions By identifying a limitation of the current velocity framework coupled with in vivo analysis of mutant cells, we reveal a coordinated step-change in gene expression kinetics during erythropoiesis, with likely implications for many other differentiation processes.

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Gastrulation: Its Principles and Variations

Kondoh

2024

Results and Problems in Cell Differentiation

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Diverse Routes toward Early Somites in the Mouse Embryo

Abstract: Highlights d Multiple transcriptional trajectories underlie somite emergence d Outlining the in vivo molecular journey toward the anterior Tindependent somites d T does not negatively regulate Sox2 to control neural output at E8.

Cited by 55 publications

References 85 publications

Dynamics of primitive streak regression controls the fate of neuromesodermal progenitors in the chicken embryo

Dynamics of primitive streak regression controls the fate of neuromesodermal progenitors in the chicken embryo

Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation

Gastrulation: Its Principles and Variations

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