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Key Developmental Regulators Suggest Multiple Origins of Pancreatic Beta Cell Regeneration.
Zebrafish ( IF 1.4 ) Pub Date : 2020-06-12 , DOI: 10.1089/zeb.2019.1777
Hao Wang 1 , Xiangyong Wei 1 , Wenchao Shi 1 , Jianbo He 1 , Lingfei Luo 1
Affiliation  

Extensive efforts have been done to try to restore the lost β cell mass for the cure of diabetes. Animal models have been established to provide evidences of cellular origins and contextual regulators of β cell regeneration. Here, we used a zebrafish β cell ablation and regeneration model to investigate β cell neogenesis in the first few days after a near-total β cell loss. Regeneration of β cells first occurred within 7 h post-treatment. Developmental regulators such as neurod, pdx1, mnx1, and nkx2.2a were active in the regenerating β cells, while at the same time suggesting different subpopulations of regenerative cellular origins. Using Cre/loxP-based lineage tracing, we showed that intrapancreatic ductal cells resisted to give rise to regenerating β cells. Given that transdifferentiation of α cell and δ cell can regenerate β cell, here we have provided further molecular evidence highly suggesting that the regenerating β cells originate from multiple cellular origins.

中文翻译:


关键的发育调节因子表明胰腺β细胞再生的多个起源。



为了治愈糖尿病,人们已经做出了大量的努力来尝试恢复丢失的β细胞量。动物模型的建立是为了提供细胞起源和β细胞再生的背景调节因子的证据。在这里,我们使用斑马鱼 β 细胞消融和再生模型来研究 β 细胞几乎完全丧失后最初几天内的 β 细胞新生。 β细胞的再生首先发生在治疗后7小时内。发育调节因子如Neurodpdx1mnx1nkx2.2a在再生 β 细胞中活跃,同时表明再生细胞起源的不同亚群。使用基于 Cre/loxP 的谱系追踪,我们发现胰腺内导管细胞抵抗产生再生 β 细胞。鉴于α细胞和δ细胞的转分化可以再生β细胞,这里我们提供了进一步的分子证据,有力地表明再生的β细胞源自多个细胞起源。
更新日期:2020-06-12
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