Parthenogenetic haploid embryonic stem cells produce fertile mice

Wang, Haifeng; He, Zhengquan; Dong, Mingzhu; Gu, Tiantian; Luo, Guan‐Zheng; Teng, Fei; Xia, Baolong; Li, Wei; Feng, Chunjing; Li, Xin; Li, Tianda; Shuai, Ling; Fu, Rui; Wang, Liu; Wang, Xiu‐Jie; Zhao, Xiaoyang; Zhou, Qi

doi:10.1038/cr.2013.126

Cited by 37 publications

(34 citation statements)

References 10 publications

(14 reference statements)

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“…Mouse embryo collection and in vitro culture under time-lapse recording Eight-to ten-week-old C57BL/6 female mice were stimulated to superovulate by standard methods (Wan et al, 2013) and then mated with DBA2 male mice. The animal-use protocols in the present study were approved by the Animal Research Committee of the Institute of Zoology, Chinese Academy of Sciences.…”

Section: Methodsmentioning

confidence: 99%

Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq

Shi

Chen

et al. 2015

Development

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During mammalian pre-implantation embryo development, when the first asymmetry emerges and how it develops to direct distinct cell fates remain longstanding questions. Here, by analyzing single-blastomere transcriptome data from mouse and human preimplantation embryos, we revealed that the initial blastomere-toblastomere biases emerge as early as the first embryonic cleavage division, following a binomial distribution pattern. The subsequent zygotic transcriptional activation further elevated overall blastomereto-blastomere biases during the two-to 16-cell embryo stages. The trends of transcriptional asymmetry fell into two distinct patterns: for some genes, the extent of asymmetry was minimized between blastomeres (monostable pattern), whereas other genes, including those known to be lineage specifiers, showed ever-increasing asymmetry between blastomeres (bistable pattern), supposedly controlled by negative or positive feedbacks. Moreover, our analysis supports a scenario in which opposing lineage specifiers within an early blastomere constantly compete with each other based on their relative ratio, forming an inclined 'lineage strength' that pushes the blastomere onto a predisposed, yet flexible, lineage track before morphological distinction.

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Section: Methodsmentioning

confidence: 99%

Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq

Shi

Chen

et al. 2015

Development

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“…Since our previous study showed that the MII oocyte-derived phESCs lost maternal imprinting in differentially methylated regions (DMRs) during culture [8], we hypothesized that bimaternal embryos generated by injecting the haploid phESCs into MII oocytes would have improved developmental potential compared with parthenogenetic embryos, which is known to die before embryonic day 9.5 (E9.5). To investigate the potential of phESCs to produce bimaternal mice, we first established phESC lines from mouse haploid parthenogenetic blastocysts carrying a constitutively expressed green fluorescent protein (Gfp) gene (Supplementary information, Figure S1A).…”

Section: Dear Editormentioning

confidence: 99%

Birth of fertile bimaternal offspring following intracytoplasmic injection of parthenogenetic haploid embryonic stem cells

Wang

Feng

et al. 2015

Cell Res

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“…Spermatozoa were released from the cauda epididymis with forceps compressing [50] and suspended in M2 medium. ICSI was then carried out as described previously [51][52][53] with some modifications. Briefly, 10 µl of sperm suspension was added to 1 ml M2 medium supplemented with 5 µg/ml of cytochalasin B, and 15-20 mature oocytes were placed in the M2 medium for 5 min.…”

Section: Icsimentioning

confidence: 99%

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

et al. 2014

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The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization. The molecular mechanism underlying the biogenesis of this lysosome-related organelle (LRO) is still largely unknown. Here, we show that germ cell-specific Atg7-knockout mice were infertile due to a defect in acrosome biogenesis and displayed a phenotype similar to human globozoospermia; this reproductive defect was successfully rescued by intracytoplasmic sperm injections. Furthermore, the depletion of Atg7 in germ cells did not affect the early stages of development of germ cells, but at later stages of spermatogenesis, the proacrosomal vesicles failed to fuse into a single acrosomal vesicle during the Golgi phase, which finally resulted in irregular or nearly round-headed spermatozoa. Autophagic flux was disrupted in Atg7-depleted germ cells, finally leading to the failure of LC3 conjugation to Golgi apparatus-derived vesicles. In addition, Atg7 partially regulated another globozoospermia-related protein, Golgi-associated PDZ-and coiled-coil motif-containing protein (GOPC), during acrosome biogenesis. Finally, the injection of either autophagy or lysosome inhibitors into testis resulted in a similar phenotype to that of germ cell-specific Atg7-knockout mice. Altogether, our results uncover a new role for Atg7 in the biogenesis of the acrosome, and we provide evidence to support the autolysosome origination hypothesis for the acrosome.

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Parthenogenetic haploid embryonic stem cells produce fertile mice

Cited by 37 publications

References 10 publications

Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq

Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq

Birth of fertile bimaternal offspring following intracytoplasmic injection of parthenogenetic haploid embryonic stem cells

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

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