Stem cells differ in mice, monkeys, and humans
New research shows that primate cells — humans are primates — are superior to stem cells in mice. Primates have more pluripotent stem cells which can become more cell types. The study maps how pluripotency differs between mice, monkeys, and humans. For the first time, illustrating how primate development corresponds to each other.
"We identified a gene set useful for predicting the properties of human and monkey pluripotent stem cells, breaking new ground for studies that use human cells," says study author Mitinori Saitou MD PhD, professor in the department of anatomy and cell biology at the graduate school of medicine at Kyoto University, whose work is published in Nature magazine.
Only stem cells derived from early mouse embryos are known to have the ultimate pluripotency — differentiation into all cell types.
Saitou: "Mouse ES cells derived from embryos before they implant in the uterine wall, can differentiate into all three germ layers [ectoderm, mesoderm and endoderm]and germ [sex] cells. Cells from post-implantation embryos aren't as flexible.
"Human cells derived from embryos before implantation, on the other hand, are known to differentiate into each germ layer — but, not consistently in the lab. Differentiation into germ cells is something we are currently studying. But where human stem cells fit in the pluripotency spectrum has been uncertain."
"Embryo developmental mechanisms differ considerably among mammals. But research on mammalian development is almost exclusively on mouse cells because of technical convenience.
"To better use human pluripotent stem cells, it's crucial to understand which embryo stage — Embryonic Stem cells [ES] and induced Pluripotent Stem [iPS] cells — are the most similar in terms of pluripotency."
Tomonori Nakamura PhD, Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, and lead author.
Researchers made a comprehensive analysis of crab-eating monkey genes expressed during embryo development. Crab eating monkeys are close genetic relatives to humans. In order to study their embryonic stem (ES) cells, the scientists developed a technique to detect tiny amounts of gene transcription, such as found from a single cell.
The team could then identify the monkey genes that characterize embryo development. After comparing how these genes were expressed in monkey ES cells to human i Pluripotent Stem (iPS) cells, they saw similar patterns between the two species when monkey embryos were one week post implantation.
"Gene expression changes rapidly directly before and after implantation.
"Another finding — monkey embryos maintain pluripotency at least a week longer than mice after implantation.
"Altogether, primate pluripotent stem cells possess the same level of pluripotency as monkey embryos — one week after implantation."
Tomonori Nakamura PhD
The study fills in an enormous gap about human embryonic development. Evolutionary differences between mammalian species during development, could help explain why some cases of infertility occur post-implantation, perhaps how to maintain stem cell pluripotency, or even induce cells to differentiate with some precision.
The epiblast (EPI) is the origin of all somatic and germ cells in mammals, and of pluripotent stem cells in vitro. To explore the ontogeny of human and primate pluripotency, here we perform comprehensive single-cell RNA sequencing for pre- and post-implantation EPI development in cynomolgus monkeys (Macaca fascicularis). We show that after specification in the blastocysts, EPI from cynomolgus monkeys (cyEPI) undergoes major transcriptome changes on implantation. Thereafter, while generating gastrulating cells, cyEPI stably maintains its transcriptome over a week, retains a unique set of pluripotency genes and acquires properties for ‘neuron differentiation’. Human and monkey pluripotent stem cells show the highest similarity to post-implantation late cyEPI, which, despite co-existing with gastrulating cells, bears characteristics of pre-gastrulating mouse EPI and epiblast-like cells in vitro. These findings not only reveal the divergence and coherence of EPI development, but also identify a developmental coordinate of the spectrum of pluripotency among key species, providing a basis for better regulation of human pluripotency in vitro.
The paper "A developmental coordinate of pluripotency among mice, monkeys and humans" appeared 24th August 2016 in Nature, with doi: 10.1038/nature19096
Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at both undergraduate and graduate levels is complemented by numerous research centers, as well as facilities and offices around Japan and the world. For more information please see: www.kyoto-u.ac.jp/en
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Sep 6, 2016 Fetal Timeline Maternal Timeline News News Archive
New research shows that certain primate stem cells have superior pluripotency compared to
some from mice. The study maps how pluripotency differs among mice, monkeys, and humans.
Image Credit: public domain composite