Biology subjects

Sun, X.-F.

Publications and source records attributed to Sun, X.-F..

3 recordsLinked to original sources

bioRxiv2023

The Developmental Transcription Factor TBX3 Physically Engages with the Wnt/β-catenin Transcriptional Complex in Human Colorectal Cancer Cells to Regulate Metastasis Genes

Wnt signaling orchestrates gene expression in a plethora of processes during development and adult cell homeostasis via the action of nuclear {beta}-catenin. Furthermore, neoplasia of the colorectal epithelium begins with aberrant Wnt/{beta}-catenin signaling. Yet, little is known about how {beta}-catenin generates context-specific transcriptional outcomes. We have previously identified the developmental transcription factor TBX3 as a tissue-specific component of the Wnt/{beta}-catenin nuclear complex during mouse forelimb development. In this study, we show that TBX3 is present and functionally active in human colorectal cancers. TBX3s genomic binding pattern suggests a regulatory role that broadly coincides with that of Wnt/{beta}-catenin. Moreover, proteomics proximity labelling indicated that, during Wnt pathway activation, TBX3 is vicinal to several protein partners, including the transcription factors TCF/LEF and chromatin remodeling complexes which are usually found at Wnt responsive elements. Sequence and structure analysis revealed that TBX3 possesses an exposed Asp-Pro-Phe (NPF) motif predicted by AlphaFold2 Multimer to mediate direct interactions with several Wnt-activated TBX3 partners. Deletion of NPF abrogates TBX3 proximity to these partners and its ability to modulate Wnt-dependent transcription. TBX3 emerges as a key modulator of the oncogenic activity of Wnt/{beta}-catenin in colorectal cancer, and its mechanism of action exposes a novel druggable protein-interaction surface.

developmental biology↗

bioRxiv2019

Dissecting the initiation of female meiosis in the mouse at single-cell resolution

Germ cell meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, in mammals, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By comparing the signature gene expression pattern of 4 meiotic germ cell clusters, we found that the 4 cell clusters correspond to different cell status en route to meiosis progression, and therefore, our research here characterized detailed transcriptome dynamics during meiotic prophase I. Reconstructing the progression of meiosis along pseudotime, we identified several new genes and molecular pathways with potential critical roles in the mitosis/meiosis transition and early meiotic progression. Last, the heterogeneity within somatic cell populations was also discussed and different cellular states were identified. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving meiosis initiation and progression in female germ cells and ovarian somatic cells.

developmental biology↗

bioRxiv2019

Single-cell transcriptome profiling reveals dermal and epithelium cell fate decisions during embryonic hair follicle development

Characterization of the morphological structure during hair follicle development has been well documented, while the current understanding of the molecular mechanisms involved in follicle development remain limited. Here, using unbiased single-cell RNA sequencing, we analyzed 15,086 single cell transcriptome profiles from E13.5 and E16.5 fetal mice, and newborn mouse (postnatal day 0, P0) dorsal skin cells. Based on t-distributed Stochastic Neighbor Embedding (tSNE) clustering, we identified 14 cell clusters from skin cells and delineated their cell identity gene expression profiles. Pseudotime ordering analysis successfully constructed epithelium/dermal cell lineage differentiation trajectory and revealed sequential activation of key regulons involved during cell fate decisions. Along with this, intercellular communication between different cell populations were inferred based on a priori knowledge of ligand-receptor pairs. Together, our findings here provide a molecular landscape during hair follicle epithelium/dermal cell lineage fate decisions, and more importantly, recapitulate sequential activation of core regulatory transcriptional factors for different cell populations during hair follicle morphogenesis.

developmental biology↗