Santosa Munirah Mohamad, Low Blaise Su Jun, Pek Nicole Min Qian, Teo Adrian Kee Keong
Stem Cells and Diabetes Laboratory, Discovery Research Division, Institute of Molecular and Cell Biology, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore.
Stem Cells and Diabetes Laboratory, Discovery Research Division, Institute of Molecular and Cell Biology , Singapore.
Front Endocrinol (Lausanne). 2016 Jan 14;6:194. doi: 10.3389/fendo.2015.00194. eCollection 2015.
In the field of stem cell biology and diabetes, we and others seek to derive mature and functional human pancreatic β cells for disease modeling and cell replacement therapy. Traditionally, knowledge gathered from rodents is extended to human pancreas developmental biology research involving human pluripotent stem cells (hPSCs). While much has been learnt from rodent pancreas biology in the early steps toward Pdx1(+) pancreatic progenitors, much less is known about the transition toward Ngn3(+) pancreatic endocrine progenitors. Essentially, the later steps of pancreatic β cell development and maturation remain elusive to date. As a result, the most recent advances in the stem cell and diabetes field have relied upon combinatorial testing of numerous growth factors and chemical compounds in an arbitrary trial-and-error fashion to derive mature and functional human pancreatic β cells from hPSCs. Although this hit-or-miss approach appears to have made some headway in maturing human pancreatic β cells in vitro, its underlying biology is vaguely understood. Therefore, in this mini-review, we discuss some of these late-stage signaling pathways that are involved in human pancreatic β cell differentiation and highlight our current understanding of their relevance in rodent pancreas biology. Our efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology. New investigations into these signaling pathways are expected to advance our knowledge in human pancreas developmental biology and to aid in the translation of stem cell biology in the context of diabetes treatments.
在干细胞生物学和糖尿病领域，我们以及其他研究人员致力于获取成熟且功能完备的人类胰腺β细胞，用于疾病建模和细胞替代疗法。传统上，从啮齿动物身上获取的知识被拓展应用于涉及人类多能干细胞（hPSC）的人类胰腺发育生物学研究。虽然在向Pdx1(+)胰腺祖细胞发育的早期阶段，我们从啮齿动物胰腺生物学中已经学到了很多知识，但对于向Ngn3(+)胰腺内分泌祖细胞的转变却知之甚少。从本质上讲，胰腺β细胞发育和成熟的后期步骤至今仍不清楚。因此，干细胞与糖尿病领域的最新进展依赖于以任意的试错方式对众多生长因子和化合物进行组合测试，以从hPSC中获得成熟且功能完备 的人类胰腺β细胞。尽管这种碰运气的方法似乎在体外使人类胰腺β细胞成熟方面取得了一些进展，但其潜在生物学机制仍了解甚少。因此，在本综述中，我们讨论了一些参与人类胰腺β细胞分化的后期信号通路，并强调了我们目前对它们在啮齿动物胰腺生物学中的相关性的理解。我们在此所做的努力揭示了几条新的信号通路，可进一步研究以阐明啮齿动物胰腺生物学中未被探索的方面。对这些信号通路的新研究有望增进我们对人类胰腺发育生物学的认识，并有助于在糖尿病治疗背景下推动干细胞生物学的转化。
