Peking University team cooperates to study new progress in human germ cell development

Peking University team cooperates to study new progress in human germ cell development

May 08, 2017 Source: Xinhuanet

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On April 27th, the team of Professor Qiao Jie from Peking University Third Hospital teamed up with the team of Tang Fuzhong, a researcher at the Peking University School of Life Sciences, to publish the latest research results online in Cell Stem Cell. The results of this research are the latest developments in the team's series of studies around human germ cells and embryonic developmental mechanisms.

It is understood that human fertility has shown a significant downward trend on a global scale. Modern assisted reproductive technology has helped many infertile couples to successfully obtain healthy offspring, but even with the most advanced technical treatment, the average live birth rate at home and abroad is only 35%. Many difficult cases experience multiple cycles and long years of repetition. Treatment, still not a successful pregnancy, "not pregnant, can not hold, not good" is a great problem for many couples of childbearing age. How to effectively solve infertility is of great significance to the stability of the family and society. The main factor that constrains the improvement of success rate is that humans have limited understanding of the molecular mechanisms regulating germ cell and normal development of embryos. Germ cells (sperms and eggs) are the seeds and ties that humans sustain their lives and pass on from generation to generation. How are these special cells different from other cells? What are the characteristics of gene expression regulation? What genetic sequences and epigenetic memories are shared by the grandparents and their parents to the offspring? Which epigenetic memory information must be cleared? Humans still lack a deep understanding of these issues.

It is reported that Professor Qiao Jie's team worked closely with the team of Tang Fuzhong researchers. Since 2010, a series of studies have been carried out around the mechanism of human germ cells and embryo development, and major breakthroughs have been made. Later, the team published further research on the development mechanism of human primordial germ cells and preimplantation embryos in "Nature", "Cell, Cell Research" and other magazines, and found key genes and epigenetics regulating embryonic and germ cell development. The regulatory features reveal that human epigenetic memory (DNA methylation markers) will undergo large-scale erasure during the development of offspring, but a large number of methylation remains on some specific repetitive elements. These findings are of great importance, whether the safety assessment of assisted reproductive technology, reproductive endocrine and metabolic diseases can be inherited to offspring or inherited hereditary, recurrent miscarriage or embryonic cessation, and clinically relevant diseases of germ cell dysplasia. The impact is far-reaching.

Recently, the team published "Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions" in the "Cell Stem Cell" magazine, systematically expounding human embryonic germ cells and their microenvironment. Gene expression profile and its regulatory mechanism during cell development.

It is reported that the study has carried out a comprehensive, systematic and in-depth analysis and interpretation of the transcriptome of human embryonic germ cells and their microenvironmental cells during the five-month developmental critical period from 4 weeks to 26 weeks of gestation, and through subsequent functions. The experiment systematically analyzed the key features such as the distribution and localization of germ cells in the gonads and the precise proportional relationship between the subpopulations of cells. The main findings are as follows: 1) After colonization into the gonads, human female and male embryonic germ cells have undergone four or two key developmental stages, respectively, and their development is a complex and orderly asynchronous process, and phase specificity is determined. Genes; 2) Identification of key microenvironment cells and their gene transcriptional and surface markers, signaling pathway activity and core transcription factor networks affecting germ cell development; 3) BMP and NOTCH between embryonic germ cells and gonadal microenvironment cells The signaling pathways are mutually regulated to synergistically maintain the stability and continuity of gonadal development. 4) It is found that the precise dynamic balance between rapid synthesis and timely degradation of retinoic acid plays an important role in regulating the entry of human female germ cells into meiosis.

This study deepens understanding of a series of key reproductive biology processes such as mitosis, meiosis, follicular development, cell migration, sex differentiation, and germ cell-microenvironment cell interaction in human germ cells, especially The understanding of the interaction and synergistic regulation mechanisms of germline-non-germline cells during gonadal development. The developmental process of human embryonic germ cells under normal physiological conditions in this study lays a foundation for the establishment of germ cell in vitro maturation and culture system, and provides a target for the diagnosis and treatment of germ cell related diseases.

Ph.D. students Li Li and Dong Wei from Peking University School of Life Sciences and Dr. Yan Liying from the Reproductive Medicine Center of Peking University Third Hospital are the first authors of the paper. Professor Qiao Jie and Tang Fuzhong are co-authors of the paper. The research was funded by the National Natural Science Foundation of China, the National Basic Research Program, the Beijing Municipal Science and Technology Commission, the National High Technology Research and Development Program, the Beijing Future Gene Diagnosis High-tech Innovation Center, and the Peking University-Tsinghua Joint Center. (Text / Peking University Third Hospital Yang Dongping)

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