Department of Stem Cell Biology, Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark; DanStem, University of Copenhagen, 3B Blegdamsvej, 2200 Copenhagen N, Denmark.
DanStem, University of Copenhagen, 3B Blegdamsvej, 2200 Copenhagen N, Denmark.
Stem Cell Reports. 2017 Oct 10;9(4):1246-1261. doi: 10.1016/j.stemcr.2017.08.009. Epub 2017 Sep 14.
The production of insulin-producing β cells from human embryonic stem cells (hESCs) in vitro represents a promising strategy for a cell-based therapy for type 1 diabetes mellitus. To explore the cellular heterogeneity and temporal progression of endocrine progenitors and their progeny, we performed single-cell qPCR on more than 500 cells across several stages of in vitro differentiation of hESCs and compared them with human islets. We reveal distinct subpopulations along the endocrine differentiation path and an early lineage bifurcation toward either polyhormonal cells or β-like cells. We uncover several similarities and differences with mouse development and reveal that cells can take multiple paths to the same differentiation state, a principle that could be relevant to other systems. Notably, activation of the key β-cell transcription factor NKX6.1 can be initiated before or after endocrine commitment. The single-cell temporal resolution we provide can be used to improve the production of functional β cells.
从人胚胎干细胞（hESCs）体外生成产生胰岛素的β细胞代表了一种用于 1 型糖尿病的细胞治疗的有前途的策略。为了探索内分泌祖细胞及其后代的细胞异质性和时间进展，我们对 hESC 体外分化的多个阶段的 500 多个细胞进行了单细胞 qPCR，并将其与人类胰岛进行了比较。我们沿着内分泌分化途径揭示了不同的亚群，并在早期出现了向多激素细胞或β样细胞的谱系分支。我们揭示了与小鼠发育的一些相似和不同之处，并发现细胞可以通过多种途径到达相同的分化状态，这一原则可能与其他系统相关。值得注意的是，关键的β细胞转录因子 NKX6.1 的激活可以在内分泌分化之前或之后开始。我们提供的单细胞时间分辨率可用于改善功能性β细胞的生成。
