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   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    The speed of life: A zoo of cells to study developmental time    
      
     Date:   
         June 20, 2023   
     Source:   
         European Molecular Biology Laboratory   
     Summary:   
         Researchers have used an unprecedented stem cell zoo to compare   
         six different mammalian species and their developmental time.   
      
      
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   FULL STORY   
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   In humans, pregnancy lasts around nine months. In mice, only 20 days,   
   and in rhinoceroses, as long as 17 months. Although many mammalian   
   species go through the same stages during embryo development, the speed   
   of development differs substantially across animals. Another example   
   of an event that differs in time across species is the formation of the   
   vertebrate body axis, the spine. The formation of the body segments that   
   will give rise to the vertebrae and ribs, called somites, is controlled   
   by a mechanism called segmentation clock. The segmentation clock is a   
   group of genes that oscillates. Each oscillation controls the formation   
   of a pair of somites. The frequency of the oscillations differs across   
   species, taking two to three times longer in humans compared to mice.   
      
   The segmentation clock is a convenient system to study differences in   
   species, and the Ebisuya group has been studying it for a long time,   
   recently revealing that thedifferences in biochemical reaction speeds are   
   responsible for the differences in the mouse and human clocks. However,   
   in order to establish whether this is a general principle of development,   
   researchers needed to broaden the species that have been studied, which   
   up to now has been relatively limited to human and mouse.   
      
   Now, researchers from the Ebisuya Group have recapitulated in the lab   
   the segmentation clock of four novel mammalian species, in addition to   
   mouse and human: marmoset, rabbit, cattle and rhinoceros. This work   
   has been done in collaboration with research groups based in Europe,   
   Japan and the United States.   
      
   What is a stem cell zoo?  A stem cell zoo is like a library of stem   
   cells from several species to study and compare different developmental   
   events. The collaboration group collected embryonic stem cells and induced   
   pluripotent stem cells from marmoset, rabbit, cattle and rhinoceros, which   
   added to the already existing library of human and mouse. This diverse   
   sampling of species is unprecedented for developmental studies, and aims   
   to constitute a platform for comparison of developmental processes.   
      
   "We wanted to create a platform of cells from several mammalian species   
   to study why their developmental time is different. We wanted to have as   
   wide a range as possible, so we chose species with body weights spanning   
   from 50 grams to 2 tonnes, gestation lengths from 20 days to 17 months,   
   and three different evolutionary histories or phylogenies: Primates   
   (human and marmoset), Glires (mouse and rabbit) and Ungulates (cattle   
   and rhino)." said Jorge La'zaro, pre- doctoral student at Ebisuya Group   
   and first author of the paper.   
      
   The group focused on studying the differences in the segmentation   
   clock of the four new species. They applied experimental protocols to   
   differentiate the embryonic and induced pluripotent stem cells into   
   pre-somitic mesoderm like cells, the cells that will give rise to the   
   spine, ribs and skeleton muscles.   
      
   "Our stem cell zoo serves as an ideal platform to investigate the cause of   
   interspecies differences in the segmentation clock period, as well as to   
   determine whether there is any general relationship between segmentation   
   tempo and the characteristics of the organism." said Miki Ebisuya, Group   
   Leader at EMBL Barcelona and at the Cluster of Excellence Physics of Life,   
   TU Dresden.   
      
   Correlating the segmentation clock The gestation length, as well as   
   many other bodily parameters are known to scale with the animal body   
   weight. Larger species tend to have a longer gestation period. The   
   group thus hypothesized that the differences in the segmentation clock   
   could be related to body weight. However, surprisingly they found no   
   correlation between the average body weight of each of the species and   
   its segmentation clock period. Similarly, the gestation length did not   
   correlate with the segmentation clock period.   
      
   Instead, the group found that the segmentation clock period was highly   
   correlated with the duration of embryogenesis. Embryogenesis is the time   
   between fertilisation until the end of organogenesis, when all organs   
   are formed in an embryo. This could mean that the segmentation clock can   
   serve as a good system to understand how general embryonic developmental   
   time is established across species.   
      
   Furthermore, the group found that the three different evolutionary   
   histories - - Primates, Glires and Ungulates -, corresponded with slow,   
   fast and intermediate segmentation clock periods respectively, pointing   
   to a relation between developmental tempo and evolutionary groups.   
      
   In previous studies, the Ebisuya group already found thatbiochemical   
   reaction speeds scale with the segmentation clock period. However,   
   those studies focused on mice and human. The group has now extended the   
   species under study and has confirmed that the four new mammals also   
   show differences in the biochemical reactions speeds, correlating very   
   well with the segmentation clock period.   
      
   That indicates that changes in the biochemical rates might be a general   
   mechanism to control developmental tempo.   
      
   Moreover, they found that genes related to biochemical processes show an   
   expression pattern that correlates with the segmentation clock period,   
   providing a concrete clue for a potential molecular mechanism underlying   
   the differences in developmental speeds across species.   
      
   "Our aim is to keep adding species in our stem cell zoo," said   
   Ebisuya. "If we want to confirm whether the findings of our research   
   could constitute a universal principle of mammalian development, we need   
   to expand the zoo and include a wider range of species and phylogenies."   
   In the current study published in Cell Stem Cell, the group focused   
   on the segmentation clock, but the stem cell zoo approach opens the   
   possibility to study other biological times such as the heart rate or   
   the lifespan. The more researchers know about how biological time works,   
   the more they might be able to control it. For example, in the field of   
   organoids, if one could accelerate the time required to develop organoids,   
   it could speed up regenerative medicine studies.   
      
   "Another aspect that I really like about the stem cell zoo is the   
   possibility to learn from different species outside of human and mouse,"   
   said La'zaro.   
      
   "Many animals have particular features that make them interesting to   
   study, but due to practical or ethical reasons we don't have access to   
   them in the lab.   
      
   Features like for example the size of a rhino, or the long neck of   
   giraffes.   
      
   Who knows, perhaps in our next project we can use stem cells to try to   
   understand how do giraffes develop their long neck -- and longer somites!"   
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Stem_Cells # Medical_Topics # Skin_Cancer #   
                   Prostate_Cancer   
             o Plants_&_Animals   
                   # New_Species # Developmental_Biology # Mice #   
                   Biotechnology   
       * RELATED_TERMS   
             o Stem_cell_treatments o Stem_cell o Somatic_cell   
             o Adult_stem_cell o Somatic_cell_nuclear_transfer   
             o Embryonic_stem_cell o Developmental_biology o   
             Bone_marrow_transplant   
      
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   Story Source: Materials provided by   
   European_Molecular_Biology_Laboratory. Original written by Carla   
   Manzanas. Note: Content may be edited for style and length.   
      
      
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   Journal Reference:   
      1. Jorge La'zaro, Maria Costanzo, Marina Sanaki-Matsumiya, Charles   
      Girardot,   
         Masafumi Hayashi, Katsuhiko Hayashi, Sebastian Diecke, Thomas B.   
      
         Hildebrandt, Giovanna Lazzari, Jun Wu, Stoyan Petkov, Ru"diger   
         Behr, Vikas Trivedi, Mitsuhiro Matsuda, Miki Ebisuya. A stem cell   
         zoo uncovers intracellular scaling of developmental tempo across   
         mammals. Cell Stem Cell, 2023; DOI: 10.1016/j.stem.2023.05.014   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230620113815.htm   
      
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