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Offspring Production of Ovarian Organoids Derived from Spermatogonial Stem Cells by Chromatin Architecture Reorganization

66 Pages Posted: 25 Oct 2019 Sneak Peek Status: Review Complete

See all articles by Huacheng Luo

Huacheng Luo

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Xiaoyong Li

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Geng G. Tian

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Dali Li

East China Normal University (ECNU) - Shanghai Key Laboratory of Regulatory Biology

Changliang Hou

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Xinbao Ding

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Lin Hou

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Qifeng Lyu

Shanghai Jiao Tong University (SJTU) - Shanghai Ninth People's Hospital

Yunze Yang

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Austin J. Cooney

Baylor University - Department of Molecular and Cellular Biology

Wenhai Xie

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Ji Xiong

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Hu Wang

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Xiaodong Zhao

Shanghai Jiao Tong University (SJTU) - Shanghai Center for Systems Biomedicine (SCSB)

Ji Wu

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

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Abstract

Fate determination of germline stem cells remains poorly understood at the chromatin structure level. Here, we demonstrate successful production of offspring from oocytes transdifferentiated from mouse spermatogonial stem cells (SSCs) with tracking of transplanted SSCs in vivo, single cell whole exome sequencing, and in 3D cell culture reconstitution of the process of oogenesis derived from SSCs. Furthermore, we demonstrate direct induction of germline stem cells (iGSCs) differentiated into functional oocytes by transduction of H19, Stella, and Zfp57 and inactivation of Plzf in SSCs after screening with ovarian organoids. Using high throughput chromosome conformation, we uncovered extensive chromatin reorganization during SSC conversion into iGSCs, which was highly similar to female germline stem cells. We observed that although topologically associating domains were stable during SSC conversion, chromatin interactions changed in a striking manner, altering 35% of inactive and active chromosomal compartments throughout the genome. These findings have important implications in various areas including mammalian gametogenesis, genetic and epigenetic reprogramming, biotechnology, and medicine.

Keywords: ovarian organoid, chromatin reorganization, imprinted gene, transcription factor, germline stem cell

Suggested Citation

Luo, Huacheng and Li, Xiaoyong and Tian, Geng G. and Li, Dali and Hou, Changliang and Ding, Xinbao and Hou, Lin and Lyu, Qifeng and Yang, Yunze and Cooney, Austin J. and Xie, Wenhai and Xiong, Ji and Wang, Hu and Zhao, Xiaodong and Wu, Ji, Offspring Production of Ovarian Organoids Derived from Spermatogonial Stem Cells by Chromatin Architecture Reorganization (October 23, 2019). Available at SSRN: https://ssrn.com/abstract=3474052 or http://dx.doi.org/10.2139/ssrn.3474052
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Huacheng Luo

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Xiaoyong Li

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Geng G. Tian

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Dali Li

East China Normal University (ECNU) - Shanghai Key Laboratory of Regulatory Biology

Shanghai
China

Changliang Hou

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Xinbao Ding

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Lin Hou

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Qifeng Lyu

Shanghai Jiao Tong University (SJTU) - Shanghai Ninth People's Hospital

Shanghai
China

Yunze Yang

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Austin J. Cooney

Baylor University - Department of Molecular and Cellular Biology

Houston, TX
United States

Wenhai Xie

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Ji Xiong

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Hu Wang

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education)

Shanghai
China

Xiaodong Zhao (Contact Author)

Shanghai Jiao Tong University (SJTU) - Shanghai Center for Systems Biomedicine (SCSB) ( email )

No. 800, Dongchuan Rd.
Wenxuan Medical Building
Shanghai, 200240
China

Ji Wu

Shanghai Jiao Tong University (SJTU) - Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education) ( email )

Shanghai
China

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