Science & Technology

Scientists create the first model of early human embryos from skin cells

Professor Jose Polo in front of the iBlastoids image.Credit: Monash University

For the first time, a fibroblast-derived model of the early embryo enables extensive research into the causes of very early miscarriage and the effects of toxins and drugs on early development.

An international team of scientists led by Monash University in Melbourne, Australia, has found a revolution in the study of early miscarriage, the causes of infertility, and the study of early human development, from skin cells to human embryos. Generated a model.

A team led by Professor Jose Polo has succeeded in reprogramming these fibroblasts or skin cells into a three-dimensional cell structure that morphologically and molecularly resembles a human blastocyst. Called iBlastoids, they can be used in the laboratory to model the biology of early human embryos.

Research published in NatureIs led by Professor Polo of the Institute for Biomedical Discovery and the Australian Institute of Regenerative Medicine at Monash University, with lead author Dr. Xiaodong (Ethan) Liu, PhD student Jia Ping Tan, and Australian collaborator Dr. Jennifer Zenker. Is participating. , Professor Ryan Lister of Monash University, University of Western Australia, and international collaborator, Associate Professor Owen Luckham of Duke National University, Professor Amander Clark of UCLA in the United States.


Images of iBlastoid with different cell staining.Credit: Monash University

This achievement is an important breakthrough for future research on fetal development and infertility. To date, the only way to study these first days was to use the hard-to-find and rare blastocysts obtained from in vitro fertilization procedures.

“With iBlastoids, scientists can use human blastocysts, and, importantly, on an unprecedented scale, at a very early stage of human development and infertility, birth defects, We can study some of the causes of the effects of toxins and viruses on early embryos, accelerating our understanding and the development of new treatments, “said Professor Polo.

Polo Lab has succeeded in generating iBlastoid using a technique called “nuclear reprogramming”. This allows the cellular identity of organized human skin cells, such as blastocysts, to change when placed on a 3D “jelly” scaffold called the extracellular matrix. The structure they named iBlastoids.

iBlastoids is the overall genetics of human blastocysts, including an inner cell mass-like structure composed of epiblast-like cells, surrounded by an outer layer of trophectoderm-like cells and a cavity that resembles a blastocoel. Model the structure.

In human embryos, epiblasts develop into suitable embryos and the vegetative ectoderm becomes the placenta. However, “iBlastoids are not exactly the same as blastocysts. For example, early blastocysts are surrounded by the zona pellucida, an egg-derived membrane that interacts with sperm during fertilization and later disappears. Does not have a zona pellucida because it is derived from adult fibroblasts, “he said.

iBlastoid Researcher

From left to right: Jia Tan, Jose Polo, Xiaodong (Ethan) Liu Credits: Monash University

Lead author of Nature “We could only believe that we made such a discovery if all the data were gathered and pointed to the same place,” said Dr. Xiaodong (Ethan) Liu, a postdoctoral fellow at Polo Lab.

Jia Ping Tan, co-lead author of PoloLab and a PhD student, said: “I’m really surprised that skin cells can be reprogrammed into these 3D cell structures that resemble blastocysts.”

This study is an in vitro study of human embryo modeling by the International Stem Cell Research Association, following 2017 and 2018 reports by British and Dutch scientists on the production and progress of mouse “blastoids” in vitro. Will be published when we are about to publish our guidelines. In the production of human stem cells that replicate aspects of early embryonic development. These guidelines are scheduled for earlier this year.

It is unclear whether the new guidelines will refer to the study published today in Nature. This study was the first to create an integrated stem cell model that closely mimics the important fate and spatiotemporal decisions made by early human embryos.However, in the paper published in Stem cell report In February of last year (2020), the association said: “If we could develop such a model for early human embryos, there would be great potential benefits for understanding early human development, studying biomedical sciences, and reducing the use of animal and human embryos. In research, however, guidelines for the ethical implementation of this series of work are not well defined at this time. “

Although there is no legal precedent for the use of human integrated stem cell models of blastocysts such as iBlastoids, all experiments are in accordance with Australian law and international guidelines that refer to the “Primitive Streak Rules”, Monash. Approved for human ethics at the university. Blastocysts cannot be cultured beyond the development of primitive streak that appears on the 14th day of embryogenesis.

Under these legislative recommendations, iBlastoids differ from blastocysts, but Polo Lab does not culture iBlastoids in vitro after day 11 and closely monitors the appearance of primitive streak-related genes. did.

Infertility and miscarriage can be caused by early-stage human embryos failing to implant or not progressing at the time of implantation. This happens in the first two weeks of pregnancy when a woman does not even know she is pregnant. These “silent” miscarriages are likely to account for a significant proportion of the total number of miscarriages that occur, and according to Professor Polo, iBlastoids production provides a model system that provides insight into this early stage of pregnancy. To do.

Professor Ross Copper, Dean of Monash University School of Medicine, said the findings would enable the development of improved methods of IVF, the development of embryonic gene therapy protocols, and the development of better and more beneficial screening methods for new drugs. I did. ..

“With further research and the right resources, this discovery could open up a whole new industry in Australia and internationally,” he said.

Reference: “By reprogramming fibroblasts into iBlastoids” by Xiaodong Liu, Jia Ping Tan, Jan Schröder, Asma Aberkane, John F. Ouyang, Monika Mohenska, Sue Mei Lim, Yu BY Sun, Joseph Chen, Guizhi Sun, Yichen Zhou Modeling Human Blastocysts, Daniel Poppe, Ryan Lister, Amander T. Clark, Owen JL Rackham, Jennifer Zenker, Jose M. Polo, March 17, 2021 Nature..
DOI: 10.1038 / s41586-021-03372-y

Scientists create the first model of early human embryos from skin cells Scientists create the first model of early human embryos from skin cells

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