Janet Rossant | |
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Born | Chatham, Kent, England | 13 July 1950
Alma mater | University of Cambridge, England University of Oxford, England |
Known for | Work in developmental biology, stem cells, and cell lineage |
Spouse | Alex Bain |
Children | Jennifer and Robert |
Awards | Fellow of the Royal Society, Howard Hughes International Scholar, Fellow of the Royal Society of Canada |
Scientific career | |
Thesis | Studies on determination and differentiation in the early mammalian embryo (1975) |
Janet Rossant, CC , FRS , FRSC (born 13 July 1950) [1] is a developmental biologist well known for her contributions to the understanding of the role of genes in embryo development. She is a leader in developmental biology. [2] Her current research interests focus on stem cells, molecular genetics, and developmental biology. [3] Specifically, she uses cellular and genetic manipulation techniques to study how genes control both normal and abnormal development of early mouse embryos. Rossant has discovered information on embryo development, how multiple types of stem cells are established, and the mechanisms by which genes control development. [4] In 1998, her work helped lead to the discovery of the trophoblast stem cell, which has assisted in showing how congenital anomalies in the heart, blood vessels, and placenta can occur. [4]
She is currently the President and Science Director at Gairdner, [5] a senior scientist in the Developmental & Stem Cell Biology Program, [6] the chief of research at the Hospital for Sick Children (SickKids) Research Institute in Toronto, [7] a university professor at the University of Toronto in the departments of Molecular Genetics, Obstetrics/Gynecology, Pediatrics, [6] deputy scientific director of the Canadian Stem Cell Network, [6] and the senior editor of the journal eLife . [8] In 2013, she was the president of International Society for Stem Cell Research.
Janet Rossant received her B.A. in zoology from the University of Oxford, England, in 1972, graduating with Honors 1st Class. She then earned her PhD in mammalian development from Darwin College, University of Cambridge, England, in 1976. [9]
Rossant's lab is based in Toronto, Canada, at the SickKids, and focuses on stem cell and embryonic research. [10] The lab specifically focuses on how cells in the early mouse embryos decide their fate and how this information can be applied to maintaining and differentiating embryo-derived stem cells. They then use this information to research how to change human iPS cells (induced pluripotent stem cells) into cell types that are useful for investigating human cell biology and disease. [11] Her research includes using genetic manipulation, live imaging, proteomics and single cell expression analysis to study fundamental lineage development. [10]
Rossant has won numerous awards in cell and developmental biology. Notably, she won the 2015 Gairdner Wightman Award for her work with the SickKids Research Institute. The Gairdner Foundation presented her with this award "for her outstanding scientific contributions to developmental biology and for her exceptional international leadership in stem cell biology and policy-making, and in advancing research programs for children’s illnesses." Her contributions have impacted the way we understand the human genome, congenital abnormalities, and the use of cancer drugs. Her innovation in manipulation of the mouse genome led to the mouse becoming the dominant model in understanding the function of the human genome sequence. [4]
Dr. Rossant was awarded the Ross G. Harrison Medal from the International Society of Developmental Biologists in 2013 at the 17th International Congress of Developmental Biology on 17 June in Cancun, Mexico. In this lifetime achievement award, given out once every four years, the society highlighted Rossant's impact in helping researchers understand human embryo development and stem cell origin, as well as developing the technique of introducing targeted mutations into genes of mouse embryos. [12]
Rossant has called attention to the immense contributions of female scientists, and was one of five women to win the 2018 L’Oréal-UNESCO For Women in Science Award. [13] In response to the award, Rossant stated, "I hope to use this opportunity to encourage more girls globally to take up careers in science, math, engineering and medicine. The future is theirs to grasp." [14]
More publications may be accessed at PubMed.
Embryonic Research
Rossant's research in cell reprogramming has built a foundation for proteomic stem cell resources, and given researchers new methods to understand the mechanisms that regulate cell fate specification. This research identified cell surface markers to monitor cellular differentiation of embryonic (ES), epiblast (EpiSC), trophoblast (TS), and extraembryonic endoderm (XEN) stem cell lineages. [15]
Stem Cell Research
A notable segment of Rossant's research has been her work leading to the 1998 discovery of the trophoblast stem cell. [4] Her work led to the ability to isolate permanent trophoblast stem cell lineages using fibroblast growth factor 4 (FGF4) in contact with mouse blastocysts or early postimplantation trophoblasts. These trophoblast lineages are crucial for the survival of the mammalian embryo in utero. [16]
Rossant's work on mice lung tissue is also very significant. Her work focused on using pluripotent stem cells to create lung epithelial tissue in mice, and examining the potential effects of these results in human medicine. This information was intended to benefit the current understanding of the pluripotent stem cell, as well as examining the potential of these cells in future regenerative medicine, discovering new facets of lung diseases, and improving treatment of lung diseases. [17]
Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development, the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently forms the embryo, and an outer layer of trophoblast cells called the trophectoderm. This layer surrounds the inner cell mass and a fluid-filled cavity or lumen known as the blastocoel. In the late blastocyst, the trophectoderm is known as the trophoblast. The trophoblast gives rise to the chorion and amnion, the two fetal membranes that surround the embryo. The placenta derives from the embryonic chorion and the underlying uterine tissue of the mother. The corresponding structure in non-mammalian animals is an undifferentiated ball of cells called the blastula.
The trophoblast is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the placenta. They form during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg to become extraembryonic structures that do not directly contribute to the embryo. After blastulation, the trophoblast is contiguous with the ectoderm of the embryo and is referred to as the trophectoderm. After the first differentiation, the cells in the human embryo lose their totipotency because they can no longer form a trophoblast. They become pluripotent stem cells.
Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the inner cell mass (embryoblast) using immunosurgery results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage have the same moral considerations as embryos in the post-implantation stage of development.
A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans produce two or three primary germ layers. Some animals, like cnidarians, produce two germ layers making them diploblastic. Other animals such as bilaterians produce a third layer between these two layers, making them triploblastic. Germ layers eventually give rise to all of an animal's tissues and organs through the process of organogenesis.
Embryoid bodies (EBs) are three-dimensional aggregates formed by pluripotent stem cells. These include embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC)
Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.
Sir Martin John EvansFLSW is an English biologist who, with Matthew Kaufman, was the first to culture mice embryonic stem cells and cultivate them in a laboratory in 1981. He is also known, along with Mario Capecchi and Oliver Smithies, for his work in the development of the knockout mouse and the related technology of gene targeting, a method of using embryonic stem cells to create specific gene modifications in mice. In 2007, the three shared the Nobel Prize in Physiology or Medicine in recognition of their discovery and contribution to the efforts to develop new treatments for illnesses in humans.
The inner cell mass (ICM) or embryoblast is a structure in the early development of an embryo. It is the mass of cells inside the blastocyst that will eventually give rise to the definitive structures of the fetus. The inner cell mass forms in the earliest stages of embryonic development, before implantation into the endometrium of the uterus. The ICM is entirely surrounded by the single layer of trophoblast cells of the trophectoderm.
Induced pluripotent stem cells are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Japan, who together showed in 2006 that the introduction of four specific genes, collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."
Shinya Yamanaka is a Japanese stem cell researcher and a Nobel Prize laureate. He is a professor and the director emeritus of Center for iPS Cell Research and Application, Kyoto University; as a senior investigator at the UCSF-affiliated Gladstone Institutes in San Francisco, California; and as a professor of anatomy at University of California, San Francisco (UCSF). Yamanaka is also a past president of the International Society for Stem Cell Research (ISSCR).
Fibroblast growth factor 4 is a protein that in humans is encoded by the FGF4 gene.
Gail Roberta Martin is an American biologist. She is professor emerita in the Department of Anatomy, University of California, San Francisco. She is known for her pioneering work on the isolation of pluripotent stem cells from normal embryos, for which she coined the term 'embryonic stem cells'. She is widely recognized for her work on the function of fibroblast growth factors and their negative regulators in vertebrate organogenesis. She and her colleagues made contributions to gene targeting technology.
Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum, begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency, and finally unipotency.
Immunosurgery is a method of selectively removing the external cell layer (trophoblast) of a blastocyst through a cytotoxicity procedure. The protocol for immunosurgery includes preincubation with an antiserum, rinsing it with embryonic stem cell derivation media to remove the antibodies, exposing it to complement, and then removing the lysed trophoectoderm through a pipette. This technique is used to isolate the inner cell mass of the blastocyst. The trophoectoderm's cell junctions and tight epithelium "shield" the ICM from antibody binding by effectively making the cell impermeable to macromolecules.
Elizabeth Jane Robertson is a British developmental biologist based at the Sir William Dunn School of Pathology, University of Oxford. She is Professor of Developmental Biology at Oxford and a Wellcome Trust Principal Research Fellow. She is best known for her pioneering work in developmental genetics, showing that genetic mutations could be introduced into the mouse germ line by using genetically altered embryonic stem cells. This discovery opened up a major field of experimentation for biologists and clinicians.
Directed differentiation is a bioengineering methodology at the interface of stem cell biology, developmental biology and tissue engineering. It is essentially harnessing the potential of stem cells by constraining their differentiation in vitro toward a specific cell type or tissue of interest. Stem cells are by definition pluripotent, able to differentiate into several cell types such as neurons, cardiomyocytes, hepatocytes, etc. Efficient directed differentiation requires a detailed understanding of the lineage and cell fate decision, often provided by developmental biology.
Magdalena Żernicka-Goetz is a Polish-British developmental biologist. She is Professor of Mammalian Development and Stem Cell Biology in the Department of Physiology, Development and Neuroscience and Fellow of Sidney Sussex College, Cambridge. She also serves as Bren Professor of Biology and Biological Engineering at California Institute of Technology (Caltech).
Professor Maneesha Inamdar is a stem cell and developmental biologist conducting research at Bangalore, India. She is presently Director of inStem, India’s first stem cell institute. She is on deputation from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore. She is an elected fellow of the Indian Academy of Sciences and the Indian National Science Academy and a J C Bose National Fellow.
A blastoid is an embryoid, a stem cell-based embryo model which, morphologically and transcriptionally resembles the early, pre-implantation, mammalian conceptus, called the blastocyst. The first blastoids were created by the Nicolas Rivron laboratory by combining mouse embryonic stem cells and mouse trophoblast stem cells. Upon in vitro development, blastoids generate analogs of the primitive endoderm cells, thus comprising analogs of the three founding cell types of the conceptus, and recapitulate aspects of implantation on being introduced into the uterus of a compatible female. Mouse blastoids have not shown the capacity to support the development of a foetus and are thus generally not considered as an embryo but rather as a model. As compared to other stem cell-based embryo models, blastoids model the preimplantation stage and the integrated development of the conceptus including the embryo proper and the two extraembryonic tissues. The blastoid is a model system for the study of mammalian development and disease. It might be useful for the identification of therapeutic targets and preclinical modelling.