Dual Effect of Raptor on Neonatal beta Cell Proliferation and Identity Maintenance
Dual Effect of Raptor on Neonatal beta Cell Proliferation and Identity Maintenance
复制标题
Raptor 对新生儿 β 细胞增殖和身份维持的双重作用
作者：
Yanqiu Wang;Jiajun Sun;Qicheng Ni;Aifang Nie;Yanyun Gu;Shu Wang;Weizhen Zhang;Guang Ning;Weiqing Wang;Qidi Wang
Immature pancreatic β cells are highly proliferative and the expansion of β cells.during early neonatal period largely determines functional β cell mass; however the.mechanisms are poorly characterized. We generated Ngn3RapKO mice (ablation of.Raptor, an essential component of mTORC1 in Ngn3+ endocrine progenitor cells),.and found that mTORC1 was dispensable for endocrine cell lineage formation, but.specifically regulated both proliferation and identity maintenance of neonatal β cells..Ablation of Raptor in neonatal β cells led to autonomous loss of cell identity,.decelerated cell cycle progression, compromised proliferation and caused neonatal.diabetes due to inadequate establishment of functional β cell mass at P14. Completely.different from mature β cells, Raptor regulated G1/S and G2/M phase cell cycle.transition, thus permitting high proliferation rate in neonatal β cells. Moreover, Ezh2.was identified as a critical downstream target of mTORC1 in neonatal β cells, which.was responsible for G2/M phase transition and proliferation. Our discovery of the.dual effect of mTORC1 in immature β cells revealed potential target for replenishing.functional β cell pools by promoting both expansion and functional maturation of.newly-formed immature β cells.
