Institute of Insect Sciences, Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insect Pests, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310058, China.
Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China.
BMC Biol. 2023 Jun 20;21(1):143. doi: 10.1186/s12915-023-01636-9.
How stem cell populations are organized and regulated within adult tissues is important for understanding cancer origins and for developing cell replacement strategies. Paradigms such as mammalian gut stem cells and Drosophila ovarian follicle stem cells (FSC) are characterized by population asymmetry, in which stem cell division and differentiation are separately regulated processes. These stem cells behave stochastically regarding their contributions to derivative cells and also exhibit dynamic spatial heterogeneity. Drosophila FSCs provide an excellent model for understanding how a community of active stem cells maintained by population asymmetry is regulated. Here, we use single-cell RNA sequencing to profile the gene expression patterns of FSCs and their immediate derivatives to investigate heterogeneity within the stem cell population and changes associated with differentiation.
We describe single-cell RNA sequencing studies of a pre-sorted population of cells that include FSCs and the neighboring cell types, escort cells (ECs) and follicle cells (FCs), which they support. Cell-type assignment relies on anterior-posterior (AP) location within the germarium. We clarify the previously determined location of FSCs and use spatially targeted lineage studies as further confirmation. The scRNA profiles among four clusters are consistent with an AP progression from anterior ECs through posterior ECs and then FSCs, to early FCs. The relative proportion of EC and FSC clusters are in good agreement with the prevalence of those cell types in a germarium. Several genes with graded profiles from ECs to FCs are highlighted as candidate effectors of the inverse gradients of the two principal signaling pathways, Wnt and JAK-STAT, that guide FSC differentiation and division.
Our data establishes an important resource of scRNA-seq profiles for FSCs and their immediate derivatives that is based on precise spatial location and functionally established stem cell identity, and facilitates future genetic investigation of regulatory interactions guiding FSC behavior.
了解成年组织中的干细胞群体如何组织和调节对于理解癌症起源和开发细胞替代策略非常重要。哺乳动物肠道干细胞和果蝇卵巢滤泡干细胞（FSC）等范例的特征是群体不对称性，其中干细胞分裂和分化是分别调节的过程。这些干细胞在其对衍生细胞的贡献方面表现出随机性，并且还表现出动态的空间异质性。果蝇 FSCs 为理解如何通过群体不对称性维持活跃的干细胞群落提供了一个很好的模型。在这里，我们使用单细胞 RNA 测序来描绘 FSCs 及其直接衍生物的基因表达模式，以研究干细胞群体内的异质性以及与分化相关的变化。
我们描述了对预先分选的细胞群体进行单细胞 RNA 测序的研究，该群体包括 FSCs 及其相邻的细胞类型，即 escort cells (ECs) 和 follicle cells (FCs)，它们支持 FSCs 的生长。细胞类型的分配依赖于生殖腺内的前后（AP）位置。我们澄清了之前确定的 FSCs 位置，并使用空间靶向谱系研究作为进一步的确认。四个簇之间的 scRNA 图谱与从 EC 到 FC 的 AP 进展一致，随后是 FSCs 和早期 FCs。EC 和 FSC 簇的相对比例与生殖腺中这些细胞类型的流行程度非常吻合。从 EC 到 FC 的几个具有分级图谱的基因被突出为指导 FSC 分化和分裂的两个主要信号通路（Wnt 和 JAK-STAT）的反向梯度的候选效应子。
我们的数据为 FSCs 及其直接衍生物建立了一个重要的 scRNA-seq 图谱资源，该资源基于精确的空间位置和功能建立的干细胞身份，并为未来指导 FSC 行为的调节相互作用的遗传研究提供了便利。
