A5001610550- Pluripotent Stem Cells Research
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Reproductive Biology and Fertility
- Renal and related cancers
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- Animal Genetics and Reproduction
- Tissue Engineering and Regenerative Medicine
- Genetic Syndromes and Imprinting
- Hippo pathway signaling and YAP/TAZ
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- 3D Printing in Biomedical Research
- Genetics and Neurodevelopmental Disorders
- Prenatal Screening and Diagnostics
- RNA Interference and Gene Delivery
- DNA Repair Mechanisms
- Liver physiology and pathology
Center for Life Sciences
2021-2024
Tsinghua University
2021-2024
Institute of Zoology
2013-2022
University of Chinese Academy of Sciences
2013-2022
Chinese Academy of Sciences
2013-2022
State Key Laboratory of Stem Cell and Reproductive Biology
2016-2022
Abstract The pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) primed (EpiSCs), respectively. However, these two states may not sufficient to reflect the full complexity developmental potency during development. Here we report establishment self-renewing formative pluripotent (fPSCs) which manifest features poised for gastrulation. fPSCs can established from different mouse ESCs, pre-/early-gastrula epiblasts induced PSCs. Similar...
Evolutionary analyses reveal conservation and divergence of epigenetic transition during early development across mammals.
Abstract Zygotic genome activation (ZGA) marks the beginning of embryonic program for a totipotent embryo, which gives rise to inner cell mass (ICM) where pluripotent epiblast arises, and extraembryonic trophectoderm. However, how ZGA is connected first lineage segregation in mammalian embryos remains elusive. Here, we investigated role nuclear receptor (NR) transcription factors (TFs), whose motifs are highly enriched accessible from 2-cell (2C) 8-cell (8C) stages mouse embryos. We found...
Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding embryonic day 3.5 (E3.5) to E7.5 mouse. E3.5 inner cell mass (ICM), regulates ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, occupies preaccessible enhancers part opened by early-stage expressing TFs TFAP2C NR5A2....
Breast cancer amplified sequence 2 (BCAS2) is involved in multiple biological processes, including pre-mRNA splicing. However, the physiological roles of BCAS2 are still largely unclear. Here we report that specifically enriched spermatogonia mouse testes. Conditional disruption Bcas2 male germ cells impairs spermatogenesis and leads to infertility. Although appear grossly normal, spermatocytes meiosis prophase I events (recombination synapsis) rarely observed BCAS2-depleted testis. In null...
ABSTRACT N 6‐methyladenosine (m 6 A) is the most prevalent and reversible internal modification of mammalian messenger noncoding RNAs mediated by specific m A writer, reader, eraser proteins. As an methyltransferase‐like 3‐methyltransferase–like 14 (METTL14)–Wilms tumor 1–associated protein complex dynamically regulates plays important roles in diverse biologic processes. However, our knowledge about complete functions this RNA methyltransferase complex, contributions each component to...
Mammalian early embryos maintain accurate genome integrity for proper development within a programmed timeline despite constant assaults on their DNA by replication, demethylation and genetic defects transmitted from germ cells. However, how is safeguarded during mammalian embryonic remains unclear. BCAS2 (Breast Carcinoma Amplified Sequence 2), core component of the PRP19 complex involved in pre-mRNA splicing, plays an important role damage response through RPA complex, key regulator...
We previously identified a subcortical maternal complex (SCMC) that is essential for early embryogenesis and female fertility in mice. However, the molecular mechanism by which SCMC affects remains largely uncharacterized. Here, we report novel protein, zinc finger BED-type containing 3 (Zbed3), participates SCMC. Depletion of Zbed3 results reduced fecundity females, because impaired delayed development proportion mutant embryos. The loss asymmetric zygotic division abnormal distributions...
Alternative splicing expands the transcriptome and proteome complexity plays essential roles in tissue development human diseases. However, how alternative regulates spermatogenesis remains largely unknown. Here, using a germ cell-specific knockout mouse model, we demonstrated that factor
Induced pluripotent stem cells (iPSCs) have wide applications in disease modeling, personalized medicine, and tissue engineering. The generation of iPSCs from somatic via transcriptional-factor- or chemical molecule-based approaches are time-consuming inefficient. Here, a cell-reprogramming-inspired dynamically responsive hydrogel is fabricated synthetic-biology-based strategy. Human mouse (including senescent cells) efficiently reprogrammed into that exhibit key features embryonic cells....
Abstract Zygotic genome activation (ZGA) is essential for early embryonic development. However, the regulation of ZGA remains elusive in mammals. Here we report that a maternal factor TDP-43, nuclear transactive response DNA-binding protein, regulates through RNA Pol II and mouse embryogenesis. Maternal TDP-43 translocates from cytoplasm into nucleus at two-cell stage when minor to major transition occurs. Genetic deletion results embryos arrested stage. co-occupies with as large foci also...
Eras encodes a Ras-like GTPase protein that was originally identified as an embryonic stem cell-specific Ras. ERAS has been known to be required for the growth of cells and stimulates somatic cell reprogramming, suggesting its roles on mouse early development. We now report dynamic expression pattern during peri-implantation development: increases at blastocyst stage, specifically decreases in E7.5 mesoderm. In accordance with pattern, increased promotes proliferation through controlling AKT...
Pluripotent stem cells hold great promise for regenerative medicine. However, before clinical application, reproducible protocols pluripotent cell differentiation should be established. Extracellular signal-regulated protein kinase (ERK) signaling plays a central role the self-renewal of epiblast (EpiSCs), but its subsequent germ layer is still ambiguous. We proposed that ERK could modulate epiblast. PD0325901 was used to inhibit activation during embryonic and EpiSCs. Immunofluorescence,...
Alternative splicing (AS) is an important mechanism to regulate organogenesis and fertility. Breast carcinoma amplified sequence 2 (BCAS2) one of the core components PRP19 complex, a multiple function complex including splicing, it involved in initiation meiosis through regulating AS male mice. However, role BCAS2 mouse oogenesis remains largely unknown. In this study, we found that was highly expressed oocytes primordial follicles. Vasa-Cre-mediated deletion Bcas2 caused poor oocyte...
ABSTRACT Alternative splicing (AS) and alternative promoter (AP) usage expand the repertories of mammalian transcriptome profiles thus diversify gene functions. However, our knowledge about extent functions AS AP in mouse early embryogenesis remains elusive. Here, by performing whole-transcriptome profiling with high-throughput next generation sequencing, we report that extensively occurs embryonic day (E) 7.5 primary germ layers, may be involved multiple developmental processes. In...
During oocyte growth, various epigenetic modifications are gradually established, accompanied by accumulation of large amounts mRNAs and proteins. However, little is known about the relationship between meiotic progression. Here, using Gdf9-Cre to achieve oocyte-specific ablation Ehmt2 (Euchromatic-Histone-Lysine-Methyltransferase 2) from primordial follicle stage, we found that female mutant mice were infertile. Oocyte-specific knockout caused failure homologous chromosome separation...
Abstract After fertilization, zygotic genome activation (ZGA) marks the beginning of embryonic program for a totipotent embryo, which further gives rise to pluripotent lineages and extraembryonic trophectoderm after first lineage commitment. While much has been learned about pluripotency regulation, how ZGA is connected commitment in early embryos remains elusive. Here, we investigated role nuclear receptor 1 family transcription factors (TFs) mouse pre-implantation embryos, whose motifs are...
Mammalian early epiblasts at different phases are characterized by naïve, formative, and primed pluripotency states, involving extensive transcriptome changes. Here, we report that deadenylase Cnot8 of Ccr4-Not complex plays essential roles during the transition from naïve to formative state. Knock out (KO) resulted in embryonic lethality mice, but KO stem cells (ESCs) could be established. Compared with differentiated normal ESCs, highly expressed a great many genes their differentiation...