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Publication : Generation of rat forebrain tissues in mice.

First Author  Huang J Year  2024
Journal  Cell Volume  187
Issue  9 Pages  2129-2142.e17
PubMed ID  38670071 Mgi Jnum  J:349463
Mgi Id  MGI:7627864 Doi  10.1016/j.cell.2024.03.017
Citation  Huang J, et al. (2024) Generation of rat forebrain tissues in mice. Cell 187(9):2129-2142.e17
abstractText  Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.
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