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.

中文翻译：

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胚胎巨噬细胞支持人胰腺分化过程中的内分泌定型。


器官发生是一个复杂的过程，它依赖于源自微环境的外源因子和组织特异性内因子之间的动态相互作用。对于胰腺内分泌细胞，局部生态位由腺泡细胞和导管细胞以及神经元、免疫、内皮细胞和基质细胞组成。早在受孕后 6 周，就在人类胰腺中检测到造血细胞，但它们是否在人类内分泌发生过程中发挥作用仍是未知数。为了研究这一点，我们对孕中期人类胰腺进行了单核 RNA 测序 （snRNA-seq），并鉴定了广泛的造血细胞，包括两个不同的组织驻留巨噬细胞亚群。利用这一发现，我们开发了一种人胚胎干细胞衍生的内分泌-巨噬细胞类器官的共培养系统，以模拟它们在体外的相互作用 。在这里，我们表明巨噬细胞在体外支持内分泌细胞 的分化和活力并增强组织植入，突出了它们在糖尿病组织工程策略中的潜在作用。