Epigenetic Regulation of Cell Fate in Mouse Embryonic Development

Research

A single zygote gives rise to a complex organism with diverse tissues and cell types. We study how reproducible cell identities emerge from a shared genome.

Our lab investigates epigenetic control of cell-fate decisions in mouse development. We combine embryogenesis and in vitro models with genetic perturbation, single-cell multi-omics and computational analysis to resolve gene function over developmental time and distinguish cell-intrinsic from non-cell-autonomous effects.

Research Aims

Multimodal epigenetic dynamics during mouse embryogenesis

We chart chromatin accessibility, DNA methylation, histone states and enhancer-promoter interactions across developmental time at single-cell resolution.

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Diagram showing time-resolved embryo sampling, multimodal epigenetic measurements and genomic signatures at single-cell resolution.

Cis-regulatory elements in cell-fate decisions

We identify candidate enhancers and transcription factors, then test their functions with targeted perturbation and epigenome editing.

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Diagram showing screening and dCas9-based perturbation of cis-regulatory elements and transcription factors.

Intrinsic and extrinsic gene functions during mouse gastrulation

Using whole-embryo and mixed chimeras with single-cell profiling, we distinguish cell-autonomous effects from changes in cell composition and developmental timing.

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Diagram comparing whole-embryo and mixed chimeras with single-cell RNA sequencing to separate cell state, composition and timing effects.

Principal Investigator

Saifeng Cheng

Assistant Professor

Principal Investigator, Westlake University

Postdoctoral Fellow, Weizmann Institute of Science

Ph.D., Huazhong Agricultural University

Current Members

Ying Zhu

PhD student (2024-)

Bachelor degree, Shenzhen University

Shuailin Du

PhD student (2024-)

Master degree, Xiamen University

Bachelor degree, Zhejiang Chinese Medical University

Jingyi He

PhD student (2025-)

Bachelor degree, Zhejiang Normal University

Jing Qian

PhD student (2025-)

Bachelor degree, Soochow University

Shuo Wang

PhD student (2025-)

Bachelor degree, Soochow University

Weiyuan Ma

Research Assistant (2025-)

Bachelor degree, South China Agricultural University

Alumni

Jinfang Wang

Postdoctoral Fellow

PhD degree, Xiamen University

Bachelor degree, Soochow University

Qi Geng

Visiting student

Jieran Don

Research Assistant

Master degree, Sichuan Agricultural University

Bachelor degree, Sichuan University of Traditional Chinese Medicine

Publications

* Co-first author # Corresponding author

2025

  • Akhiad Bercovich, Aviezer Lifshitz, Michal Eldar, Saifeng Cheng, Roni Stok Ranen, Yonatan Stelzer, Amos Tanay#. IceQream: Quantitative chromosome accessibility analysis using physical TF models. Nature Communication 16, 8984. 10.1038/s41467-025-63925-x.

2024

  • Ron Hadas*, Hernan Rubinstein*, Markus Mittnenzweig*, Yoav Mayshar, Raz Ben-Yair, Saifeng Cheng, Alejandro Aguilera-Castrejon, Netta Reines, Ayelet-Hashahar Orenbuch, Aviezer Lifshitz, Dong-Yuan Chen, Michael B Elowitz, Magdalena Zernicka-Goetz, Jacob H Hanna, Amos Tanay#, Yonatan Stelzer#. Temporal BMP4 effects on mouse embryonic and extraembryonic development. Nature 634, 652-661. 10.1038/s41586-024-07937-5.

2023

  • Yoav Mayshar*, Ofir Raz*, Saifeng Cheng, Raz Ben-Yair, Ron Hadas, Netta Reines, Markus Mittnenzweig, Oren Ben-Kiki, Aviezer Lifshitz, Amos Tanay#, Yonatan Stelzer#. Time-aligned hourglass gastrulation models in rabbit and mouse. Cell 186, 2610-2627.e18. 10.1016/j.cell.2023.04.037.
  • Marko Dunjić*, Felix Jonas*, Gilad Yaakov*, Roye More, Yoav Mayshar, Yoach Rais, Ayelet-Hashahar Orenbuch, Saifeng Cheng, Naama Barkai, Yonatan Stelzer. Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells. Nat Commun 14, 1-19. 10.1038/s41467-023-39477-3.
  • Saifeng Cheng, Yoav Mayshar, Yonatan Stelzer. Induced epigenetic changes memorized across generations in mice. Cell 186, 683-685. 10.1016/j.cell.2023.01.023.

2022

  • Saifeng Cheng*, Markus Mittnenzweig*, Yoav Mayshar, Aviezer Lifshitz, Marko Dunjić, Yoach Rais, Raz Ben-Yair, Stephanie Gehrs, Elad Chomsky, Zohar Mukamel, Hernan Rubinstein, Katharina Schlereth, Netta Reines, Ayelet-Hashahar Orenbuch, Amos Tanay#, Yonatan Stelzer#. The intrinsic and extrinsic effects of TET proteins during gastrulation. Cell 185, 3169-3185.e20.

2021

  • Markus Mittnenzweig*, Yoav Mayshar*, Saifeng Cheng, Raz Ben-Yair, Ron Hadas, Yoach Rais, Elad Chomsky, Netta Reines, Anna Uzonyi, Lior Lumerman, Aviezer Lifshitz, Zohar Mukamel, Ayelet-Hashahar Orenbuch, Amos Tanay#, Yonatan Stelzer#. A single-embryo, single-cell time-resolved model for mouse gastrulation. Cell 184, 2825-2842.e22. 10.1016/j.cell.2021.04.004.
  • Alejandro Aguilera-Castrejon*, Bernardo Oldak*, Tom Shani, Nadir Ghanem, Chen Itzkovich, Sharon Slomovich, Shadi Tarazi, Jonathan Bayerl, Valeriya Chugaeva, Muneef Ayyash, Shahd Ashouokhi, Daoud Sheban, Nir Livnat, Lior Lasman, Sergey Viukov, Mirie Zerbib, Yoseph Addadi, Yoach Rais, Saifeng Cheng, Yonatan Stelzer, Hadas Keren-Shaul, Raanan Shlomo, Rada Massarwa, Noa Novershtern, Itay Maza#, Jacob H Hanna#. Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis. Nature 593, 119-124. 10.1038/s41586-021-03416-3.

2018

  • Saifeng Cheng, Feng Tan, Yue Lu, Xiaoyun Liu, Tiantian Li, Wenjia Yuan, Yu Zhao, Dao-Xiu Zhou. WOX11 recruits a histone H3K27me3 demethylase to promote gene expression during shoot development in rice. Nucleic Acids Res 46, 2356-2369. 10.1093/nar/gky017.
View all publications on Google Scholar

We are recruiting

Find your place in Cheng Lab

Postdocs · Graduate students · Research assistants · Visiting students

Postdoctoral researcher

Good fit if

  • You have a PhD and a strong background in developmental biology, epigenetics, single-cell genomics, computational biology or a related field.
  • Experience in mouse embryology or gene editing is especially welcome.

How to apply

Email your CV, a brief description of your research interests and contact information for three references.

Graduate student

Good fit if

  • You want to study how cell identities and gene regulation change during development.
  • You are preparing to apply through the Westlake University graduate program and are interested in a lab rotation.

How to apply

Apply through the Westlake University graduate program and email us your CV and a short introduction to your research interests.

Research assistant

Good fit if

  • You are curious about developmental biology, epigenetics, single-cell genomics or computational biology.
  • Practical laboratory or data-analysis experience is helpful, but motivation and ability to learn matter most.

How to apply

Email your CV, research interests, relevant experience and expected availability.

Visiting student

Good fit if

  • Your interests connect with developmental biology, epigenetics, single-cell measurements or computational analysis.
  • You have a focused learning or research goal that can be developed with the lab.

How to apply

Email your CV, research interests and your proposed visit timing and duration.

Not sure where you fit?

Tell us about your background and interests.

Email the lab
3-228/229, Yunqi Campus, Westlake University, Hangzhou, China