通过转录因子导向的分化,通过快速的人类 oogonia-like 细胞特异化
Merrick Pierson Smela1,2, Christian C Kramme3,4, Patrick R J Fortuna1,2
1Wyss Institute, Harvard Medical School, Boston, MA, USA.
EMBO reports
|January 23, 2025
概括
科学家们确定了五种转录因子 (TF),它们在短短四天内将人类诱导的多能干细胞 (hiPSC) 快速转化为类似 oogonia 的细胞 (iOLC),从而加速了体外游戏生成研究.
科学领域:
- 干细胞生物学 干细胞生物学
- 生殖生物学 生殖生物学
- 发育生物学是发展生物学.
背景情况:
- 从人类诱导的多能干细胞 (hiPSCs) 生成生殖细胞对于体外生殖过程至关重要.
- 以前的方法需要长时间的细胞培养,如3D有机体共培养大约四个月.
研究的目的:
- 确定转录因子 (TFs),可以快速将hiPSC转化为类似 oogonia 的细胞 (iOLC).
- 改善从hiPSCs中生产的人类原始生殖细胞类细胞 (hPGCLCs) 的生产.
- 为研究人类体外 oogenesis.建立新的工具.
主要方法:
- 使用高通量选管道来识别TF的组合.
- 在无料单层条件下的hiPSC中共同表达了五个特定的TF (ZNF281,LHX8,SOHLH1,ZGLP1和ANHX).
- 表达了DLX5,HHEX和FIGLA以增强hPGCLC的生产.
主要成果:
- 在短短四天内成功生成了具有高效率的DDX4阳性iOLC.
- 证明了从hiPSCs中提高hPGCLCs的生产.
- 使用基因和蛋白质表达分析特征iOLCs和hPGCLCs,证实它们与内源性生殖细胞的相似性.
结论:
- 鉴定出新的调控因素,可显著增强人体胚胎细胞在体外的特异性.
- 开发了快速高效的方法,从hiPSCs中产生类似于oogonia的和原始的生殖细胞的细胞.
- 建立了有价值的计算和实验工具,以推进人类体外 oogenesis 研究.
更多相关视频
12:06Generation of Human Primordial Germ Cell-like Cells at the Surface of Embryoid Bodies from Primed-pluripotency Induced Pluripotent Stem Cells
Published on: January 11, 2019
12.3K
09:47Differentiation of Newborn Mouse Skin Derived Stem Cells into Germ-like Cells In vitro
Published on: July 16, 2013
9.2K
相关概念视频
Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K
Cellular Differentiation
2.5K
How does a complex organism such as a human develop from a single cell? It all starts from a single fertilized egg which gives rise to a vast array of cell types, such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.
A zygote is a...
A zygote is a...
2.5K
Oogenesis
1.0K
Oogenesis, the process of developing egg cells (female gametes), occurs within the ovaries and is fundamental to female fertility. This sequence begins during fetal development when diploid oogonia in the developing ovaries undergo mitotic divisions to produce primary oocytes. By birth, these primary oocytes enter prophase I of meiosis but become arrested in this stage, remaining suspended until puberty.
Each primary oocyte is surrounded by a layer of pre-granulosa cells, forming what is...
Each primary oocyte is surrounded by a layer of pre-granulosa cells, forming what is...
1.0K
Somatic to iPS Cell Reprogramming
2.2K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K
Determination
18.1K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
18.1K
Forced Transdifferentiation
1.9K
Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial...
Artificial...
1.9K
