Developmental Cell Lineages

Our bodies are built of >30 trillion cells specialized to fulfill diverse roles within our tissues, organs, and organ systems. All these cells originate from a single cell, a zygote formed at conception. From zygote to fetus, and throughout childhood, adolescence, and adulthood, cells divide and commit to different fates in order for the organism to develop, sustain and regenerate. The series of steps that lead from an undifferentiated progenitor cell, such as a stem cell, to one of its several possible specialized descendants constitutes a cell lineage path (Burgess et al. 2018). Cell lineage paths are organized by organ systems. Each cell lineage path cross-references a Gene Ontology (GO) biological process (The Gene Ontology Consortium 2019), and consists of a series of causally connected cell development steps. Cell development steps describe the transition between cell states during development or differentiation and are characterized by regulators (molecules promoting or inhibiting the step) and, when established, “required input components” (cell state biomarkers required for the action of regulators). Each cell state is characterized by a cell type defined in Cell Ontology (Sarntivijai et al. 2014; Osumi-Sutherland 2017), anatomical location from UBERON (Haendel et al. 2014), and a unique combination of protein and/or RNA markers with references, when available, to CellMarker (Hu et al. 2023) and PanglaoDB (Franzen et al. 2019). For a more detailed data model description, please refer to Milacic et al. 2024. Recent technological advances have allowed researchers to harvest high-throughput omics data from single cells of multicellular organisms and use it to track and manipulate cell fates (Burgess 2018; Saelens et al. 2019). This opens the door to the possibility of deciphering cell lineage paths at single-cell resolution, a critical requirement for the advancement of regenerative medicine and cancer medicine.<br><br>The cell lineage path “Differentiation of keratinocytes in interfollicular epidermis in mammalian skin” describes the differentiation of keratinocytes from stem cells to corneocytes in the interfollicular epidermis, the skin surface layer in between the adnexa (hair follicles, sweat glands, and sebaceous glands).

我们的身体由超过三百万亿个细胞构成，这些细胞在组织、器官及器官系统中承担着多样化的功能。所有这些细胞均源自一个单一的细胞，即受精时形成的受精卵。从受精卵到胎儿，以及在整个儿童期、青春期和成年期，细胞不断进行分裂并选择不同的命运，以使生物体得以发育、维持和再生。从未分化祖细胞，例如干细胞，到其多个潜在分化后代的系列步骤构成了细胞谱系路径（Burgess 等人，2018年）。细胞谱系路径按器官系统进行组织，并与基因本体（Gene Ontology，GO）生物过程进行交叉引用（The Gene Ontology Consortium，2019年），包括一系列因果相连的细胞发育步骤。细胞发育步骤描述了发育或分化过程中细胞状态的转变，其特征在于调节因子（促进或抑制步骤的分子）以及在建立后，“必需输入成分”（调节因子作用所需的细胞状态生物标志物）。每个细胞状态均由细胞本体（Cell Ontology）中定义的细胞类型、来自 UBERON（Haendel 等人，2014年）的解剖学位置，以及蛋白质和/或 RNA 标记的独特组合所表征，如有参考资料，则涉及 CellMarker（Hu 等人，2023年）和 PanglaoDB（Franzen 等人，2019年）。欲了解更多详细的数据模型描述，请参阅 Milacic 等人（2024年）。近期技术进步使得研究人员能够从多细胞生物的单个细胞中收集高通量组学数据，并利用这些数据追踪和操纵细胞命运（Burgess，2018年；Saelens 等人，2019年）。这为在单细胞分辨率下解码细胞谱系路径开启了大门，这对于再生医学和癌症医学的发展至关重要。《哺乳动物皮肤毛囊间表皮中角质形成细胞的分化》这一细胞谱系路径描述了角质形成细胞从干细胞到毛囊间表皮角质细胞的分化过程，这是位于毛囊（毛发生长点）、汗腺和皮脂腺之间的皮肤表层。