Offspring production of haploid spermatid-like cells derived from mouse female germline stem cells with chromatin condensation

Xiaopeng Hu,Shangang Li,Hu Wang,Geng G Tian,Bo Xu,Yongqiang Zhao,Changliang Hou,Ji Wu,Xinyue Li,Lin He,Qian Fang,Xinyan Zhao,Xuejin Chen

doi:10.1186/s13578-021-00697-z

Abstract

BackgroundDuring male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs).ResultsWe found that spermatogenesis was restarted by transplanting FGSCs into Kitw/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kitw/wv mutant mice, cytokines and retinoic acid. Healthy offspring were produced by sperm and SLCs derived from the in vivo and in vitro transdifferentiation of FGSCs, respectively. Furthermore, high-throughput chromosome conformation capture sequencing(Hi-C-seq) and “bivalent” (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis.ConclusionThis study demonstrates that sperm can be produced from FGSCs without a Y chromosome. This suggests a strategy for dairy cattle breeding to produce only female offspring with a high-quality genetic background.

Highlights

Spermatogenesis depends on the stem cell niche and microenvironment created by testicular somatic cells andMany studies have shown that the microenvironment and epigenetics are closely related and that they interact with each other
These results indicated that Female germline stem cells (FGSCs) in seminiferous tubules can transdifferentiate into spermatogonial stem cells (SSCs) or earlystage male germ cells
Karyotype analysis confirmed the existence of haploid cells from in vitro transdifferentiation (Fig. 3E) and the fSLCs exhibited ACR localization (Fig. 3F). These results indicated that FGSCs can be induced by testicular cells, retinoic acid (RA), and cytokines to transdifferentiate into spermatid-like cells (SLCs) in vitro

Summary

Introduction

Spermatogenesis depends on the stem cell niche and microenvironment created by testicular somatic cells andMany studies have shown that the microenvironment and epigenetics are closely related and that they interact with each other. Enzymes that regulate epigenetics can promote DNA transcription and post-translational modifications, thereby affecting the expression of metabolism-related genes [6]. The Y chromosome can form perfect pairing with the X chromosome It is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs). Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kitw/wv mutant mice, cytokines and retinoic acid. High-throughput chromosome conformation capture sequencing(Hi-C-seq) and “bivalent” (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis

Methods

Results

Discussion

Conclusion