哺乳动物发育中的第一个细胞命运分支的生成模型
Maria Avdeeva1, Madeleine Chalifoux2,3, Bradley Joyce3
1Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, NY 10010, USA.
概括
研究人员开发了实时成像来模拟早期哺乳动物的发育,揭示了YAP蛋白质动力学如何推动细胞命运决定的特罗菲克托德尔姆 (TE) 和内部细胞质量 (ICM) 谱系之间. 这项工作阐明了细胞特异的随机性质及其对未来发育阶段的影响.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 系统生物学 系统生物学
背景情况:
- 哺乳动物胚胎的初始细胞命运决定区分了皮 (TE) 和内部细胞质 (ICM) 血统.
- 这种关键的分支是通过在异步细胞分裂过程中YAP转录协同激活器的亚细胞局部化来调节的.
- 在固定的胚胎中分析TE/ICM规范动力学是具有挑战性的,因为囊胚异步和排列.
研究的目的:
- 开发和应用一种活体成像方法来量化早期哺乳动物发育中的细胞命运动态.
- 使用YAP,CDX2和SOX2动态构建了第一个细胞命运分支的生成模型.
- 研究TE/ICM细胞分配中的随机性和时间异质性及其发育意义.
主要方法:
- 植入前胚胎的实时成像,以追踪核YAP定位和目标基因CDX2 (TE标记物) 和SOX2 (ICM标记物) 的表达.
- 测量YAP,CDX2和SOX2.2的双向动态.
- 开发一个生成模型来分析TE/ICM细胞分配统计和YAP动态.
主要成果:
- 该生成模型准确地预测了TE/ICM细胞分配的时间依赖统计数据.
- 该模型揭示了关键细胞命运决定因素诱导 (CDX2和SOX2) 的随机时间.
- 在ICM内SOX2表达的时间异质性突出,可能影响后续的发育决策.
结论:
- 这项研究阐明了哺乳动物发育中的第一个细胞命运决定的动态调节.
- 开发的实时成像和建模方法为剖析细胞命运选择提供了一个框架.
- 了解ICM细胞异质性对于调查后续发育事件至关重要.
相关概念视频
Determination
19.1K
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...
19.1K
Zygotic Development And Stem Cell Formation
5.5K
The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
5.5K
Gastrulation
58.6K
Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata...
58.6K
Cellular Differentiation
3.3K
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...
3.3K
Determining the Plane of Cell Division
3.4K
Positioning the cell division plane is a critical step during development and cell differentiation, particularly during mitosis when the plane is essential for determining the size of the two daughter cells. The cell division plane is perpendicular to the plane of chromosome segregation, but different types of organisms have different cell division mechanisms to suit their morphology and function.
Animal cells
In animal cells, the cleavage furrow forms along the plane of cell division...
Animal cells
In animal cells, the cleavage furrow forms along the plane of cell division...
3.4K
Cells Coordinate Growth and Proliferation
4.6K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
4.6K


