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单层平台体外生成和纯化原始生殖样细胞，为人类生殖系特化提供了新视角。

Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification.

机构信息

Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, 94305, USA.

出版信息

Nat Commun. 2023 Sep 14;14(1):5690. doi: 10.1038/s41467-023-41302-w.

DOI:10.1038/s41467-023-41302-w
PMID:37709760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10502105/
Abstract

Generating primordial germ cell-like cells (PGCLCs) from human pluripotent stem cells (hPSCs) advances studies of human reproduction and development of infertility treatments, but often entails complex 3D aggregates. Here we develop a simplified, monolayer method to differentiate hPSCs into PGCs within 3.5 days. We use our simplified differentiation platform and single-cell RNA-sequencing to achieve further insights into PGCLC specification. Transient WNT activation for 12 h followed by WNT inhibition specified PGCLCs; by contrast, sustained WNT induced primitive streak. Thus, somatic cells (primitive streak) and PGCLCs are related-yet distinct-lineages segregated by temporally-dynamic signaling. Pluripotency factors including NANOG are continuously expressed during the transition from pluripotency to posterior epiblast to PGCs, thus bridging pluripotent and germline states. Finally, hPSC-derived PGCLCs can be easily purified by virtue of their CXCR4PDGFRAGARP surface-marker profile and single-cell RNA-sequencing reveals that they harbor transcriptional similarities with fetal PGCs.

摘要

从人类多能干细胞 (hPSC) 中生成原始生殖细胞样细胞 (PGCLC) 可推进人类生殖和不孕治疗的研究，但通常需要复杂的 3D 聚集体。在这里，我们开发了一种简化的单层方法，可在 3.5 天内将 hPSC 分化为 PGCLC。我们使用简化的分化平台和单细胞 RNA 测序，进一步深入了解 PGCLC 的特化。短暂的 WNT 激活 12 小时，随后抑制 WNT 可指定 PGCLC；相比之下，持续的 WNT 诱导原始条纹。因此，体细胞（原始条纹）和 PGCLC 是由时间动态信号分隔的相关但不同的谱系。多能性因子包括 NANOG 在从多能性到后原肠胚到 PGCLC 的过渡过程中持续表达，从而连接多能性和生殖系状态。最后，hPSC 衍生的 PGCLC 可通过其 CXCR4+PDGFRα+GARP 表面标志物特征轻松纯化，单细胞 RNA 测序表明它们与胎儿 PGCLC 具有转录相似性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/c9e3f8ec3f5e/41467_2023_41302_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/671e20a12b70/41467_2023_41302_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/f7fb575a3d3f/41467_2023_41302_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/809059c0fed6/41467_2023_41302_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/59f298bc01ec/41467_2023_41302_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/5184d8418a8e/41467_2023_41302_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/b1f17e6cce9b/41467_2023_41302_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/3491c2b8cc46/41467_2023_41302_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/41a9e6e4ccd6/41467_2023_41302_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/c9e3f8ec3f5e/41467_2023_41302_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/671e20a12b70/41467_2023_41302_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/f7fb575a3d3f/41467_2023_41302_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/809059c0fed6/41467_2023_41302_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/59f298bc01ec/41467_2023_41302_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/5184d8418a8e/41467_2023_41302_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/b1f17e6cce9b/41467_2023_41302_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/3491c2b8cc46/41467_2023_41302_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/41a9e6e4ccd6/41467_2023_41302_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10502105/c9e3f8ec3f5e/41467_2023_41302_Fig9_HTML.jpg

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