加拿大多伦多大学Maria Cristina Nostro等研究人员合作发现，胚胎期巨噬细胞在人体胰腺分化过程中支持内分泌功能的确立。相关论文于2024年10月14日在线发表于国际学术期刊《细胞—干细胞》。

研究人员表示，器官发生是一个复杂的过程，依赖于来自微环境的外部因素与组织特异性内部因素之间的动态相互作用。对于胰腺内分泌细胞而言，其局部环境包括腺泡细胞、导管细胞以及神经、免疫、内皮和间质细胞。在人类胰腺中，造血细胞在受孕后6周就已被检测到，但它们是否在内分泌发生过程中发挥作用仍然未知。

为了解这一点，研究人员对孕中期人类胰腺进行了单核RNA测序（snRNA-seq），并鉴定出广泛的造血细胞类型，包括两种不同亚型的组织驻留巨噬细胞。基于这一发现，研究人员开发了一种人类胚胎干细胞衍生的内分泌-巨噬细胞类器官共培养系统，以在体外模拟它们的相互作用。

该研究表明，巨噬细胞在体外支持内分泌细胞的分化和存活，并增强了组织移植的成功率，突显了其在糖尿病组织工程策略中的潜在作用。

附：英文原文

Title: Embryonic macrophages support endocrine commitment during human pancreatic differentiation

Author: Adriana Migliorini, Sabrina Ge, Michael H. Atkins, Amanda Oakie, Rangarajan Sambathkumar, Gregory Kent, Haiyang Huang, Angel Sing, Conan Chua, Adam J. Gehring, Gordon M. Keller, Faiyaz Notta, Maria Cristina Nostro

Issue&Volume: 2024-10-14

Abstract: Organogenesis is a complex process that relies on a dynamic interplay between extrinsic factors originating from the microenvironment and tissue-specific intrinsic factors. For pancreatic endocrine cells, the local niche consists of acinar and ductal cells as well as neuronal, immune, endothelial, and stromal cells. Hematopoietic cells have been detected in human pancreas as early as 6 post-conception weeks, but whether they play a role during human endocrinogenesis remains unknown. To investigate this, we performed single-nucleus RNA sequencing (snRNA-seq) of the second-trimester human pancreas and identified a wide range of hematopoietic cells, including two distinct subsets of tissue-resident macrophages. Leveraging this discovery, we developed a co-culture system of human embryonic stem cell-derived endocrine-macrophage organoids to model their interaction in vitro. Here, we show that macrophages support the differentiation and viability of endocrine cells in vitro and enhance tissue engraftment, highlighting their potential role in tissue engineering strategies for diabetes.

DOI: 10.1016/j.stem.2024.09.011

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00325-4