The beta (β)-cell mass formed during embryogenesis is amplified by cell replication during fetal and early postnatal development. Thereafter, β cells become functionally mature, and their mass is maintained by a low rate of replication. For those few β cells that replicate in adult life, it is not known how replication is initiated nor whether this occurs in a specialized subset of β cells. We capitalized on a YAP overexpression system to induce replication of stem-cell-derived β cells and, by single-cell RNA sequencing, identified an upregulation of the leukemia inhibitory factor (LIF) pathway. Activation of the LIF pathway induces replication of human β cells in vitro and in vivo. The expression of the LIF receptor is restricted to a subset of transcriptionally distinct human β cells with increased proliferative capacity. This study delineates novel genetic networks that control the replication of LIF-responsive, replication-competent human β cells.

中文翻译：

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鉴定人β细胞的LIF反应性，复制能力亚群。

胚胎形成过程中形成的β（β）细胞团在胎儿和出生后早期发育过程中被细胞复制放大。此后，β细胞功能成熟，并且其质量通过低复制率得以维持。对于成年后能复制的少数β细胞，尚不清楚复制是如何开始的，也不知道复制是否会在专门的β细胞亚群中发生。我们利用YAP过表达系统来诱导干细胞衍生的β细胞复制，并通过单细胞RNA测序确定了白血病抑制因子（LIF）途径的上调。LIF途径的激活在体外和体内诱导人β细胞的复制。LIF受体的表达仅限于转录能力增强的转录上不同的人β细胞的一部分。