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人雄激素源性诱导多能干细胞的生成。

Generation of human androgenetic induced pluripotent stem cells.

机构信息

Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, 05029, Republic of Korea.

Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, 05029, Republic of Korea.

出版信息

Sci Rep. 2020 Feb 27;10(1):3614. doi: 10.1038/s41598-020-60363-1.

DOI:10.1038/s41598-020-60363-1
PMID:32109236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7046633/
Abstract

In humans, parthenogenesis and androgenesis occur naturally in mature cystic ovarian teratomas and androgenetic complete hydatidiform moles (CHM), respectively. Our previous study has reported human parthenogenetic induced pluripotent stem cells from ovarian teratoma-derived fibroblasts and screening of imprinted genes using genome-wide DNA methylation analysis. However, due to the lack of the counterparts of uniparental cells, identification of new imprinted differentially methylated regions has been limited. CHM are inherited from only the paternal genome. In this study, we generated human androgenetic induced pluripotent stem cells (AgHiPSCs) from primary androgenetic fibroblasts derived from CHM. To investigate the pluripotency state of AgHiPSCs, we analyzed their cellular and molecular characteristics. We tested the DNA methylation status of imprinted genes using bisulfite sequencing and demonstrated the androgenetic identity of AgHiPSCs. AgHiPSCs might be an attractive alternative source of human androgenetic embryonic stem cells. Furthermore, AgHiPSCs can be used in regenerative medicine, for analysis of genomic imprinting, to study imprinting-related development, and for disease modeling in humans.

摘要

在人类中，孤雌生殖和雄核生殖分别自然发生在成熟的囊性卵巢畸胎瘤和雄性完全性葡萄胎中。我们之前的研究已经报道了从卵巢畸胎瘤衍生的成纤维细胞中诱导产生的人类孤雌生殖多能干细胞，并使用全基因组 DNA 甲基化分析筛选印迹基因。然而，由于缺乏单亲细胞的对应物，新的印迹差异甲基化区域的鉴定受到限制。CHM 仅从父本基因组遗传。在这项研究中，我们从 CHM 的原发性雄性胚胎瘤衍生的成纤维细胞中生成了人类雄性生殖诱导多能干细胞 (AgHiPSCs)。为了研究 AgHiPSCs 的多能性状态，我们分析了它们的细胞和分子特征。我们使用亚硫酸氢盐测序分析了印迹基因的 DNA 甲基化状态，并证明了 AgHiPSCs 的雄性生殖特性。AgHiPSCs 可能是人类雄性生殖胚胎干细胞的一种有吸引力的替代来源。此外，AgHiPSCs 可用于再生医学、基因组印迹分析、研究印迹相关发育以及在人类中进行疾病建模。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/6bcf1a49962c/41598_2020_60363_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/c0cbd4fb670e/41598_2020_60363_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/b71e6cb97cc1/41598_2020_60363_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/acd0a5564a5e/41598_2020_60363_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/9ae8b84b06e8/41598_2020_60363_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/6bcf1a49962c/41598_2020_60363_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/c0cbd4fb670e/41598_2020_60363_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/b71e6cb97cc1/41598_2020_60363_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/acd0a5564a5e/41598_2020_60363_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/9ae8b84b06e8/41598_2020_60363_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/7046633/6bcf1a49962c/41598_2020_60363_Fig5_HTML.jpg

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本文引用的文献

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Alteration of Genomic Imprinting Status of Human Parthenogenetic Induced Pluripotent Stem Cells during Neural Lineage Differentiation.人孤雌生殖诱导多能干细胞在神经谱系分化过程中基因组印记状态的改变
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Novel imprinted single CpG sites found by global DNA methylation analysis in human parthenogenetic induced pluripotent stem cells.
通过全基因组 DNA 甲基化分析在人类孤雌诱导多能干细胞中发现的新型印迹单 CpG 位点。
Epigenetics. 2018;13(4):343-351. doi: 10.1080/15592294.2018.1460033. Epub 2018 May 3.
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