Temporal transcriptomic profiling reveals dynamic changes in gene expression of Xenopus animal cap upon activin treatment

Abstract

Activin, a member of the transforming growth factor-β (TGF-β) superfamily of proteins, induces various tissues from the amphibian presumptive ectoderm, called animal cap explants (ACs) in vitro. However, it remains unclear how and to what extent the resulting cells recapitulate in vivo development. To comprehensively understand whether the molecular dynamics during activin-induced ACs differentiation reflect the normal development, we performed time-course transcriptome profiling of Xenopus ACs treated with 50 ng/mL of activin A, which predominantly induced dorsal mesoderm. The number of differentially expressed genes (DEGs) in response to activin A increased over time, and totally 9857 upregulated and 6663 downregulated DEGs were detected. 1861 common upregulated DEGs among all Post_activin samples included several Spemann’s organizer genes. In addition, the temporal transcriptomes were clearly classified into four distinct groups in correspondence with specific features, reflecting stepwise differentiation into mesoderm derivatives, and a decline in the regulation of nuclear envelop and golgi. From the set of early responsive genes, we also identified the suppressor of cytokine signaling 3 (socs3) as a novel activin A-inducible gene. Our transcriptome data provide a framework to elucidate the transcriptional dynamics of activin-driven AC differentiation, reflecting the molecular characteristics of early normal embryogenesis.

Quantitative analysis of transcriptome dynamics provides novel insights into developmental state transitions

“…This is consistent with a role for BMP signaling in actively ventralizing mesoderm and other tissues [ 104 ]. We compared our endoderm and ventral mesoderm trajectories to a recently published Activin-induced mesoderm time series [ 6 ] and found that the Activin treated samples cluster more closely relative to BMP4/7 treated samples (Fig. S 5 B).…”

“…These cells-inner cell mass cells in mammals and naïve animal pole cells in amphibians-can give rise to the derivative cell types of all three germ layers and as such can recapitulate the path to different lineage states including the relevant gene regulatory network (GRN) topology and dynamics. Studies using explants of pluripotent cells from Xenopus blastulae (so called "animal caps") have been central to our current understanding of the signals and transcriptional responses that direct these stem cells toward specific lineage states [2][3][4][5][6]. Some of these signals emanate from the blastopore lip, or the Spemann-Mangold organizer, and help to direct formation and patterning of the primary germ layers [7][8][9].…”

Quantitative Analysis of Transcriptome Dynamics Provides Novel Insights into Developmental State Transitions

“…These cells-inner cell mass cells in mammals and naïve animal pole cells in amphibians-can give rise to the derivative cell types of all three germ layers and as such can recapitulate the path to different lineage states including the relevant gene regulatory network (GRN) topology and dynamics. Studies using explants of pluripotent cells from Xenopus blastulae (so called “animal caps”) have been central to our current understanding of the signals and transcriptional responses that direct these stem cells toward specific lineage states (Snape et al 1987, Ariizumi and Asashima 2001, Ariizumi et al 2009, Ariizumi et al 2017, Satou-Kobayashi et al 2021). Some of these signals emanate from the blastopore lip, or the Spemann-Mangold organizer, and help to direct formation and patterning of the primary germ layers (Spemann & Mangold 1924, Harland & Gerhart 1997, Niehrs 2004).…”