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Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization

INTRODUCTION: Fate determination of germline stem cells remains poorly understood at the chromatin structure level. OBJECTIVES: Our research hopes to develop successful offspring production of ovarian organoids derived from spermatogonial stem cells (SSCs) by defined factors. METHODS: The offspring...

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Autores principales: Luo, Huacheng, Li, Xiaoyong, Tian, Geng G., Li, Dali, Hou, Changliang, Ding, Xinbao, Hou, Lin, Lyu, Qifeng, Yang, Yunze, Cooney, Austin J., Xie, Wenhai, Xiong, Ji, Wang, Hu, Zhao, Xiaodong, Wu, Ji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463929/
https://www.ncbi.nlm.nih.gov/pubmed/34603780
http://dx.doi.org/10.1016/j.jare.2021.03.006
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author Luo, Huacheng
Li, Xiaoyong
Tian, Geng G.
Li, Dali
Hou, Changliang
Ding, Xinbao
Hou, Lin
Lyu, Qifeng
Yang, Yunze
Cooney, Austin J.
Xie, Wenhai
Xiong, Ji
Wang, Hu
Zhao, Xiaodong
Wu, Ji
author_facet Luo, Huacheng
Li, Xiaoyong
Tian, Geng G.
Li, Dali
Hou, Changliang
Ding, Xinbao
Hou, Lin
Lyu, Qifeng
Yang, Yunze
Cooney, Austin J.
Xie, Wenhai
Xiong, Ji
Wang, Hu
Zhao, Xiaodong
Wu, Ji
author_sort Luo, Huacheng
collection PubMed
description INTRODUCTION: Fate determination of germline stem cells remains poorly understood at the chromatin structure level. OBJECTIVES: Our research hopes to develop successful offspring production of ovarian organoids derived from spermatogonial stem cells (SSCs) by defined factors. METHODS: The offspring production from oocytes transdifferentiated from mouse 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. The defined factors were screened with ovarian organoids. We uncovered extensive chromatin reorganization during SSC conversion into induced germline stem cells (iGSCs) using high throughput chromosome conformation. RESULTS: We demonstrate successful production of offspring from oocytes transdifferentiated from mouse spermatogonial stem cells (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. 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. CONCLUSION: We demonstrate successful offspring production of ovarian organoids derived from SSCs by defined factors with chromatin reorganization. These findings have important implications in various areas including mammalian gametogenesis, genetic and epigenetic reprogramming, biotechnology, and medicine.
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spelling pubmed-84639292021-10-01 Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization Luo, Huacheng Li, Xiaoyong Tian, Geng G. Li, Dali Hou, Changliang Ding, Xinbao Hou, Lin Lyu, Qifeng Yang, Yunze Cooney, Austin J. Xie, Wenhai Xiong, Ji Wang, Hu Zhao, Xiaodong Wu, Ji J Adv Res Basic and Biological Science INTRODUCTION: Fate determination of germline stem cells remains poorly understood at the chromatin structure level. OBJECTIVES: Our research hopes to develop successful offspring production of ovarian organoids derived from spermatogonial stem cells (SSCs) by defined factors. METHODS: The offspring production from oocytes transdifferentiated from mouse 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. The defined factors were screened with ovarian organoids. We uncovered extensive chromatin reorganization during SSC conversion into induced germline stem cells (iGSCs) using high throughput chromosome conformation. RESULTS: We demonstrate successful production of offspring from oocytes transdifferentiated from mouse spermatogonial stem cells (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. 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. CONCLUSION: We demonstrate successful offspring production of ovarian organoids derived from SSCs by defined factors with chromatin reorganization. These findings have important implications in various areas including mammalian gametogenesis, genetic and epigenetic reprogramming, biotechnology, and medicine. Elsevier 2021-03-17 /pmc/articles/PMC8463929/ /pubmed/34603780 http://dx.doi.org/10.1016/j.jare.2021.03.006 Text en © 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Basic and Biological Science
Luo, Huacheng
Li, Xiaoyong
Tian, Geng G.
Li, Dali
Hou, Changliang
Ding, Xinbao
Hou, Lin
Lyu, Qifeng
Yang, Yunze
Cooney, Austin J.
Xie, Wenhai
Xiong, Ji
Wang, Hu
Zhao, Xiaodong
Wu, Ji
Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
title Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
title_full Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
title_fullStr Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
title_full_unstemmed Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
title_short Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
title_sort offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
topic Basic and Biological Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463929/
https://www.ncbi.nlm.nih.gov/pubmed/34603780
http://dx.doi.org/10.1016/j.jare.2021.03.006
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