Smriti Sanchita, Class of 2020
Amander Clark is the Professor and Chair of the Department of Molecular, Cell and Developmental biology in the Division of Life Sciences at University of California, Los Angeles. Dr Clark’s lab specializes in reproductive developmental biology and seeks to understand the cellular and molecular basis of germline cell differentiation. In layman terms, germ cells can be defined as sperm and egg. Dr Clark’s lab works on human primordial germ cells (hPGCs) which serve as precursors to human germ cells. The stages of development of these germ cells is still not clearly understood around the world. Due to this knowledge gap, underlying causes of human infertility remains in the dark. Dr Clark’s lab aims to study the development of human germ cells in order to define the “normal” mechanism for development of these cells. Identifying the “normal” can help her and everyone in the field understand what “abnormal” is. Eventually, they hope to see alterations in the development of these germ cells in infertile humans, and potentially develop treatments to target this deficit in humans.
Scientifically, the most effective model to study hPGC development would be a human embryo. However, due to ethical issues, Dr Clark’s lab has to utilize an alternative model. Legally, scientists can only grow out human embryos up toDr Day 14 of development. Due to this short time frame, it is difficult to effectively study the growth of hPGCs in a human embryo. Thus, Dr Clark’s lab uses established stem cell lines as a model for the whole system of hPGCs.
In a recent study, the Clark lab differentiated human embryonic stem cells (hESCs) into hPGCs and ran assays to study gene regulation. Upon using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) to identify regions of open chromatin in hPGCs, they found a transcription factor TFAP2C which serves a crucial role in hPGC formation. They found that the TFAP2C-regulated OCT4 naive enhancer is intricately involved in hPGC formation. In order to confirm their findings, they used CRISPR/Cas9 to delete the TFAP2C-bound naive enhancer at the OCT4 locus, which resulted in impaired hPGC development.
This finding by the Clark lab solved a part of the puzzle of normal germ cell development in human embryos. By establishing the normal expression of genes in these hPGCs, they can identify the various upregulated or downregulated genes which lead to human infertility. This information is crucial to develop gene therapy models to rebuild tissues and restore fertility in both humans who are born with this defect as well as those who lose fertility due to severe illnesses such as cancer.
Scientifically, the most effective model to study hPGC development would be a human embryo. However, due to ethical issues, Dr Clark’s lab has to utilize an alternative model. Legally, scientists can only grow out human embryos up toDr Day 14 of development. Due to this short time frame, it is difficult to effectively study the growth of hPGCs in a human embryo. Thus, Dr Clark’s lab uses established stem cell lines as a model for the whole system of hPGCs.
In a recent study, the Clark lab differentiated human embryonic stem cells (hESCs) into hPGCs and ran assays to study gene regulation. Upon using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) to identify regions of open chromatin in hPGCs, they found a transcription factor TFAP2C which serves a crucial role in hPGC formation. They found that the TFAP2C-regulated OCT4 naive enhancer is intricately involved in hPGC formation. In order to confirm their findings, they used CRISPR/Cas9 to delete the TFAP2C-bound naive enhancer at the OCT4 locus, which resulted in impaired hPGC development.
This finding by the Clark lab solved a part of the puzzle of normal germ cell development in human embryos. By establishing the normal expression of genes in these hPGCs, they can identify the various upregulated or downregulated genes which lead to human infertility. This information is crucial to develop gene therapy models to rebuild tissues and restore fertility in both humans who are born with this defect as well as those who lose fertility due to severe illnesses such as cancer.
Proudly powered by Weebly