Tu Lab

Tatdn2 is required for DNA repair to safeguard genome stability in primordial germ cells

Fri, 19 Dec 2025 00:00:00 +0000

Maintaining genome integrity in germ cells is crucial for fertility and species survival. However, the DNA repair mechanisms that sustain genome integrity in primordial germ cells (PGCs), which cope with high levels of replication stress, remain largely unknown. While the TatD family of proteins, evolutionarily conserved nucleases, has been found to play roles in various DNA-related processes, their in vivo functions in vertebrates have yet to be fully elucidated. TATDN2 has recently been implicated in resolving R-loops and participating in the replication stress response in BRCA1-deficient cancer cells. Here we found that tatdn2 exhibits conserved expression in mitotic and early meiotic germ cells across teleosts and mammals. Using medaka fish as a model, we then showed that loss of tatdn2 leads to all-phenotypically male adults and infertility due to PGC depletion during mitotic proliferation. We further demonstrated that knockout of tatdn2 increases R-loop accumulation and DNA damage, subsequently triggering apoptosis in PGCs. These findings indicate that tatdn2 plays a critical role in DNA damage repair associated with R-loop resolution in mitotic PGCs. Our study provides novel insights into the physiological function of TATDN2 and the mechanisms of genome maintenance in PGCs.

祝贺汉桥第一篇 tatdn2 文章发表！

Fri, 19 Dec 2025 00:00:00 +0000

全国斑马鱼研究大会-兰州

Mon, 18 Aug 2025 00:00:00 +0000

祝贺蒋璞玄获得 Tulab 2024 年度特别贡献奖

Fri, 14 Feb 2025 00:00:00 +0000

祝贺璞玄在青年学者论坛获奖

Thu, 30 Jan 2025 00:00:00 +0000

全国发育生物学大会-郑州

Mon, 02 Sep 2024 00:00:00 +0000

祝贺鹤荣完成博士论文答辩！

Fri, 31 May 2024 00:00:00 +0000

恭喜实验室诞生科二代！

Wed, 28 Feb 2024 00:00:00 +0000

祝贺璞玄获得 Tulab 2023 年度特别贡献奖

Fri, 23 Feb 2024 00:00:00 +0000

祝贺汉桥获得研究究所优秀个人

Wed, 31 Jan 2024 00:00:00 +0000

From Understudied to Understood: Multi-Omics Analysis with MiniENCODE Exemplified by Zebrafish

Mon, 01 Jan 2024 00:00:00 +0000

Abstract: The ENCODE project provides a comprehensive map of genomic activity in humans and mice. However, its extensive toolbox can be too costly and technically challenging for smaller research communities. This presents a hurdle for understudied model organisms where resource constraints and complex omics data integration further compound the challenge. To bridge this gap, our study introduces a miniENCODE project, using the zebrafish as an exemplar. We collected, generated and integrated datasets from three experimental assays across developmental stages and adult tissues. This analysis is facilitated by our newly developed miniODP database, a computational tool designed for the integration and visualization of multi-omics data. Utilizing these methods, we have cataloged over 52,000 candidate enhancers, identified various stage-specific, tissue-specific, and constantly active enhancers, and experimentally validated a subset of heart-specific enhancers. We have delineated key transcription factors and their corresponding regulatory networks across developmental stages and adult tissues. This study not only delivers valuable regulatory insights for the zebrafish research community but also illustrates how an integrative approach can aid in understanding complex regulatory mechanisms even with limited resources. This strategy could empower scientific communities working with various understudied model organisms to expedite their genomic research without overstretching their resources.Competing Interest StatementThe authors have declared no competing interest.

Single-Cell Transcriptome Analysis of the Germ Cells and Somatic Cells during Mitotic Quiescence Stage in Goats

Thu, 30 Nov 2023 00:00:00 +0000

Abstract: The mitotic quiescence of prospermatogonia is the event known to occur during genesis of the male germline and is tied to the development of the spermatogenic lineage. The regulatory mechanisms and the functional importance of this process have been demonstrated in mice; however, regulation of this process in human and domestic animal is still largely unknown. In this study, we employed single-cell RNA sequencing to identify transcriptional signatures of prospermatogonia and major somatic cell types in testes of goats at E85, E105, and E125. We identified both common and specific Gene Ontology categories, transcription factor regulatory networks, and cell-cell interactions in cell types from goat testis. We also analyzed the transcriptional dynamic changes in prospermatogonia, Sertoli cells, Leydig cells, and interstitial cells. Our datasets provide a useful resource for the study of domestic animal germline development.

Tulab in 2023

Fri, 10 Nov 2023 00:00:00 +0000

NFIB Facilitates Replication Licensing by Acting as a Genome Organizer

Mon, 21 Aug 2023 00:00:00 +0000

Abstract: The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes.

游览京东大峡谷

Wed, 16 Aug 2023 00:00:00 +0000

祝贺杨航完成博士论文答辩！

Mon, 14 Aug 2023 00:00:00 +0000

全国斑马鱼研究大会青岛

Mon, 07 Aug 2023 00:00:00 +0000

祝贺晓雪完成博士论文答辩！

Tue, 16 May 2023 00:00:00 +0000

Universal Beijing

Wed, 19 Oct 2022 00:00:00 +0000

祝贺莹姝获得国家自然科学基金青年项目

Fri, 30 Sep 2022 00:00:00 +0000

祝贺莹姝获得中国博士后科学基金

Thu, 30 Jun 2022 00:00:00 +0000

祝贺勇杰完成博士论文答辩！

Fri, 20 May 2022 00:00:00 +0000

A Small-Molecule Cocktail Promotes Mammalian Cardiomyocyte Proliferation and Heart Regeneration

Thu, 07 Apr 2022 00:00:00 +0000

Abstract: Zebrafish and mammalian neonates possess robust cardiac regeneration via the induction of endogenous cardiomyocyte (CM) proliferation, but adult mammalian hearts have very limited regenerative potential. Developing small molecules for inducing adult mammalian heart regeneration has had limited success. We report a chemical cocktail of five small molecules (5SM) that promote adult CM proliferation and heart regeneration. A high-content chemical screen, along with an algorithm-aided prediction of small-molecule interactions, identified 5SM that efficiently induced CM cell cycle re-entry and cytokinesis. Intraperitoneal delivery of 5SM reversed the loss of heart function, induced CM proliferation, and decreased cardiac fibrosis after rat myocardial infarction. Mechanistically, 5SM potentially targets α1 adrenergic receptor, JAK1, DYRKs, PTEN, and MCT1 and is connected to lactate-LacRS2 signaling, leading to CM metabolic switching toward glycolysis/biosynthesis and CM de-differentiation before entering the cell-cycle. Our work sheds lights on the understanding CM regenerative mechanisms and opens therapeutic avenues for repairing the heart.

Evolutionarily Conservative and Non-Conservative Regulatory Networks during Primate Interneuron Development Revealed by Single-Cell RNA and ATAC Sequencing

Thu, 10 Mar 2022 00:00:00 +0000

Abstract: The differences in size and function between primate and rodent brains, and the association of disturbed excitatory/inhibitory balance with many neurodevelopmental disorders highlight the importance to study primate ganglionic eminences (GEs) development. Here we used single-cell RNA and ATAC sequencing to characterize the emergence of cell diversity in monkey and human GEs where most striatal and cortical interneurons are generated. We identified regional and temporal diversity among progenitor cells which give rise to a variety of interneurons. These cells are specified within the primate GEs by well conserved gene regulatory networks, similar to those identified in mice. However, we detected, in human, several novel regulatory pathways or factors involved in the specification and migration of interneurons. Importantly, comparison of progenitors between our human and published mouse GE datasets led to the discovery and confirmation of outer radial glial cells in GEs in human cortex. Our findings reveal both evolutionarily conservative and nonconservative regulatory networks in primate GEs, which may contribute to their larger brain sizes and more complex neural networks compared with mouse.

祝贺勇杰、杨航获得 Tulab 2021 年度特别贡献奖。

Fri, 18 Feb 2022 00:00:00 +0000

Tulab in 2021

Fri, 26 Nov 2021 00:00:00 +0000

祝贺雪梅完成博士论文答辩！

Wed, 12 May 2021 00:00:00 +0000

Single-Cell Immune Landscape of Human Recurrent Miscarriage

Fri, 30 Apr 2021 00:00:00 +0000

Abstract: Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage (RM). However, an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking. In this study, we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation. Integrative analysis identifies 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed. Specifically, the cytotoxic properties of CD8+ effector T cells, nature killer (NK), and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status, and the population proportions and ligand-receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients. The molecular features, spatial distribution, and the developmental trajectories of five decidual NK (dNK) subsets have been elaborately illustrated. In RM patients, a dNK subset that supports embryonic growth is diminished in proportion, while the ratio of another dNK subset with cytotoxic and immune-active signature is significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subset substantially accumulates in RM decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

An interview by Nature Methods

Wed, 24 Feb 2021 00:00:00 +0000

祝贺莹姝获得国家奖学金、中科院院长优秀奖、振声奖学金优秀奖！

Thu, 31 Dec 2020 00:00:00 +0000

祝贺TuLab 获得遗传发育所2020年度优秀团队！

Thu, 24 Dec 2020 00:00:00 +0000

祝贺屠老师获2020年度遗传发育所益海嘉里优秀导师奖！

Wed, 25 Nov 2020 00:00:00 +0000

祝贺莹姝完成博士论文答辩，我们实验室毕业的第一位博士！

Wed, 18 Nov 2020 00:00:00 +0000

发育生物学大会广州

Thu, 29 Oct 2020 00:00:00 +0000

Happy Teachers' Day

Thu, 10 Sep 2020 00:00:00 +0000

Welcome Back!

Fri, 03 Jul 2020 00:00:00 +0000

Dynamic transcriptional and chromatin accessibility landscape of medaka embryogenesis

Fri, 26 Jun 2020 00:00:00 +0000

Website:

http://tulab.genetics.ac.cn/medaka_omics/

Download:

Citation:

Li Y, Liu Y, Yang H, Zhang T, Naruse K, Tu Q. 2020. Dynamic transcriptional and chromatin accessibility landscape of medaka embryogenesis. Genome Res 30: 924–937. [DOI]

Here we report a dynamic transcriptome landscape of medaka embryogenesis profiled by long-read RNA-seq, short-read RNA-seq, and ATAC-seq. Integrating these datasets, we constructed a much-improved gene model set including about 17,000 novel isoforms and identified 1600 transcription factors, 1100 long non-coding RNAs, and 150,000 potential cis-regulatory elements as well. We built a user-friend medaka omics data portal to present these datasets. This resource provides the first comprehensive omics datasets of medaka embryogenesis. We term these three assays as the minimum ENCODE toolbox and propose the use of it as the initial and essential profiling genomic assays for model organisms that have limited data available. This work will be of great value for the research community using medaka as the model organism and many others as well.

Dynamic Transcriptional and Chromatin Accessibility Landscape of Medaka Embryogenesis

Fri, 26 Jun 2020 00:00:00 +0000

Abstract: Medaka (Oryzias latipes) has become an important vertebrate model widely used in genetics, developmental biology, environmental sciences, and many other fields. A high-quality genome sequence and a variety of genetic tools are available for this model organism. However, existing genome annotation is still rudimentary, as it was mainly based on computational prediction and short-read RNA-seq data. Here we report a dynamic transcriptome landscape of medaka embryogenesis profiled by long-read RNA-seq, short-read RNA-seq, and ATAC-seq. Integrating these datasets, we constructed a much-improved gene model set including about 17,000 novel isoforms, identified 1600 transcription factors, 1100 long non-coding RNAs, and 150,000 potential cis-regulatory elements as well. Time-series datasets provided another dimension of information. With the expression dynamics of genes and accessibility dynamics of cis-regulatory elements, we investigated isoform switching, regulatory logic between accessible elements and genes during embryogenesis. We built a user-friend medaka omics data portal to present these datasets. This resource provides the first comprehensive omics datasets of medaka embryogenesis. Ultimately, we term these three assays as the minimum ENCODE toolbox and propose the use of it as the initial and essential profiling genomic assays for model organisms that have limited data available. This work will be of great value for the research community using medaka as the model organism and many others as well.

Multi-omics landscape published!文章发表，祝贺莹姝、勇杰和参与的各位成员！

Fri, 26 Jun 2020 00:00:00 +0000

Decode-seq published!文章发表，祝贺莹姝和参与的各位成员！

Mon, 23 Mar 2020 00:00:00 +0000

Decode-seq: a practical approach to improve differential gene expression analysis

Mon, 23 Mar 2020 00:00:00 +0000

Download:

Citation:

Li Y, Yang H, Zhang H, Liu Y, Shang H, Zhao H, Zhang T, Tu Q. 2020. Decode-seq: a practical approach to improve differential gene expression analysis. Genome Biol 21: 66. [DOI]

It is often the case that inadequate numbers of biological replicates are utilized in differential gene expression analysis. We describe an easy and effective RNA-seq approach using molecular barcoding to enable profiling a large number of replicates simultaneously. This approach significantly improved the performance of differential gene expression analysis. Using this approach in medaka fish (Oryzias latipes), we discovered novel genes with sexually dimorphic expression, and genes necessary for germ cell development. We appeal that the common practice of using three replicates in differential gene expression analysis should be abandoned.

Decode-Seq: A Practical Approach to Improve Differential Gene Expression Analysis

Mon, 23 Mar 2020 00:00:00 +0000

Abstract: Many differential gene expression analyses are conducted with an inadequate number of biological replicates. We describe an easy and effective RNA-seq approach using molecular barcoding to enable profiling of a large number of replicates simultaneously. This approach significantly improves the performance of differential gene expression analysis. Using this approach in medaka (Oryzias latipes), we discover novel genes with sexually dimorphic expression and genes necessary for germ cell development. Our results also demonstrate why the common practice of using only three replicates in differential gene expression analysis should be abandoned.

New Year Party 中心联欢会舞蹈秀

Tue, 31 Dec 2019 00:00:00 +0000

Autumn 秋

Tue, 26 Nov 2019 00:00:00 +0000

National Day Gathering 十一假期聚会

Mon, 30 Sep 2019 00:00:00 +0000

International Zebrafish Conference - Suzhou 国际斑马鱼大会-苏州

Sat, 15 Jun 2019 00:00:00 +0000

Meet Dr

Fri, 14 Jun 2019 00:00:00 +0000

Got Fish Facility Space, FINALLY

Fri, 30 Nov 2018 00:00:00 +0000

发育生物学大会-昆明

Tue, 16 Oct 2018 00:00:00 +0000

与钱文峰老师实验室的友好活动

Thu, 30 Aug 2018 00:00:00 +0000

欢送艳宁

Fri, 17 Nov 2017 00:00:00 +0000

莹姝参加中日美国际学生研讨会

Sat, 28 Oct 2017 00:00:00 +0000

新养殖系统

Tue, 17 Jan 2017 00:00:00 +0000

欢迎杨航、晓雪加入实验室

Fri, 26 Aug 2016 00:00:00 +0000

We moved to the new lab space

Thu, 07 Apr 2016 00:00:00 +0000

Dr

Fri, 25 Mar 2016 00:00:00 +0000

新鱼缸架

Wed, 03 Feb 2016 00:00:00 +0000

The first snow of 2015

Fri, 06 Nov 2015 00:00:00 +0000

石林峡旅行

Sat, 06 Jun 2015 00:00:00 +0000

Birthday party

Sun, 31 May 2015 00:00:00 +0000

Our first Olympic-forest-park-lab-meeting, after 5km hiking

Thu, 16 Apr 2015 00:00:00 +0000

Our first group picture

Mon, 24 Nov 2014 00:00:00 +0000

Young medaka

Wed, 15 Oct 2014 00:00:00 +0000

medaka fries

Sat, 27 Sep 2014 00:00:00 +0000

The first batch of medaka embryos arrived

Sun, 21 Sep 2014 00:00:00 +0000

TuLab is founded

Thu, 17 Jul 2014 00:00:00 +0000

Tu Lab

Tatdn2 is required for DNA repair to safeguard genome stability in primordial germ cells

祝贺汉桥第一篇 tatdn2 文章发表！

全国斑马鱼研究大会-兰州

祝贺蒋璞玄获得 Tulab 2024 年度特别贡献奖

祝贺璞玄在青年学者论坛获奖

全国发育生物学大会-郑州

祝贺鹤荣完成博士论文答辩！

恭喜实验室诞生科二代！

祝贺璞玄获得 Tulab 2023 年度特别贡献奖

祝贺汉桥获得研究究所优秀个人

From Understudied to Understood: Multi-Omics Analysis with MiniENCODE Exemplified by Zebrafish

Single-Cell Transcriptome Analysis of the Germ Cells and Somatic Cells during Mitotic Quiescence Stage in Goats

Tulab in 2023

NFIB Facilitates Replication Licensing by Acting as a Genome Organizer

游览京东大峡谷

祝贺杨航完成博士论文答辩！

全国斑马鱼研究大会 青岛

祝贺晓雪完成博士论文答辩！

Universal Beijing

祝贺莹姝获得国家自然科学基金青年项目

祝贺莹姝获得中国博士后科学基金

祝贺勇杰完成博士论文答辩！

A Small-Molecule Cocktail Promotes Mammalian Cardiomyocyte Proliferation and Heart Regeneration

Evolutionarily Conservative and Non-Conservative Regulatory Networks during Primate Interneuron Development Revealed by Single-Cell RNA and ATAC Sequencing

祝贺勇杰、杨航获得 Tulab 2021 年度特别贡献奖。

Tulab in 2021

祝贺雪梅完成博士论文答辩！

Single-Cell Immune Landscape of Human Recurrent Miscarriage

An interview by Nature Methods

祝贺莹姝获得国家奖学金、中科院院长优秀奖、振声奖学金优秀奖！

祝贺TuLab 获得遗传发育所2020年度优秀团队！

祝贺屠老师获2020年度遗传发育所益海嘉里优秀导师奖！

祝贺莹姝完成博士论文答辩，我们实验室毕业的第一位博士！

发育生物学大会 广州

Happy Teachers' Day

Welcome Back!

Dynamic transcriptional and chromatin accessibility landscape of medaka embryogenesis

Dynamic Transcriptional and Chromatin Accessibility Landscape of Medaka Embryogenesis

Multi-omics landscape published!文章发表，祝贺莹姝、勇杰和参与的各位成员！

Decode-seq published!文章发表，祝贺莹姝和参与的各位成员！

Decode-seq: a practical approach to improve differential gene expression analysis

Decode-Seq: A Practical Approach to Improve Differential Gene Expression Analysis

New Year Party 中心联欢会舞蹈秀

Autumn 秋

National Day Gathering 十一假期聚会

International Zebrafish Conference - Suzhou 国际斑马鱼大会-苏州

Meet Dr

Got Fish Facility Space, FINALLY

发育生物学大会-昆明

与钱文峰老师实验室的友好活动

欢送艳宁

莹姝参加中日美国际学生研讨会

新养殖系统

欢迎杨航、晓雪加入实验室

We moved to the new lab space

Dr

新鱼缸架

The first snow of 2015

石林峡旅行

Birthday party

Our first Olympic-forest-park-lab-meeting, after 5km hiking

Our first group picture

Young medaka

medaka fries

The first batch of medaka embryos arrived

TuLab is founded

全国斑马鱼研究大会青岛

发育生物学大会广州