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Zygotic Development And Stem Cell Formation01:10

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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...
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The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
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After a large-single-celled zygote is produced via fertilization, the process of cleavage occurs while zygotes travel through the uterine tube. Cleavage is a mitotic cell division that does not result in growth. With each round of successive cell division, daughter cells get increasingly smaller.
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Defining the Teratoma as a Model for Multi-lineage Human Development.

Daniella McDonald1, Yan Wu2, Amir Dailamy2

  • 1Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, San Diego, CA 92093, USA.

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|November 5, 2020
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Summary

Teratomas, used to validate stem cell pluripotency, can model human development. This study shows they reproducibly generate diverse cell types and enable genetic screening across all germ layers for developmental research.

Keywords:
CRISPR-Cas9barcodinggenetic circuitsgenetic screensmiRNAsmodel systemsmulti-lineage developmentsingle-cell RNA sequencingteratomatissue engineering

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Genomics

Background:

  • Teratomas are established models for validating stem cell pluripotency.
  • Understanding human developmental processes requires robust and reproducible models.

Purpose of the Study:

  • To evaluate teratomas as a platform for studying human development and genetic screening.
  • To characterize cell types and heterogeneity within teratomas.
  • To assess the utility of teratomas for functional genetic screens and tissue engineering.

Main Methods:

  • Single-cell RNA sequencing (RNA-seq) of 179,632 cells from 23 teratomas.
  • Cellular barcoding for lineage contribution analysis.
  • Pooled CRISPR-Cas9 knockout screens.
  • MicroRNA (miRNA)-regulated suicide gene expression for tissue sculpting.

Main Results:

  • Teratomas reproducibly contain ~20 cell types across all three germ layers.
  • Inter-teratoma cell type heterogeneity is comparable to organoid systems.
  • Teratoma-derived gut and brain cells resemble fetal cell types.
  • CRISPR screens enabled simultaneous genetic perturbation assays across germ layers.
  • Molecular sculpting enriched for specific tissues.

Conclusions:

  • Teratomas serve as a promising platform for multi-lineage human development modeling.
  • They facilitate pan-tissue functional genetic screening.
  • Teratomas offer potential for tissue engineering applications.