Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
PLoS One. 2024 Jan 5;19(1):e0296280. doi: 10.1371/journal.pone.0296280. eCollection 2024.
Microglia, the resident immune cells of the brain, are crucial in the development of the nervous system. Recent evidence demonstrates that microglia modulate adult hippocampal neurogenesis by inhibiting cell proliferation of neural precursors and survival both in vitro and in vivo, thus maintaining a balance between cell division and cell death in the neural stem cell pool. There are increasing reports suggesting these microglia found in neurogenic niches differ from their counterparts in non-neurogenic areas. Here, we present evidence that hippocampal microglia exhibit transcriptomic heterogeneity, with some cells expressing genes associated with neurogenesis. By comprehensively profiling myeloid lineage cells in the hippocampus using single cell RNA-sequencing, we have uncovered a small, yet distinct population of microglia which exhibit depletion in genes associated with homeostatic microglia and enrichment of genes associated with phagocytosis. Intriguingly, this population also expresses a gene signature with substantial overlap with previously characterized phenotypes, including disease associated microglia (DAM), a particularly unique and compelling microglial state.
小胶质细胞是大脑中的固有免疫细胞，在神经系统的发育中起着关键作用。最近的证据表明，小胶质细胞通过抑制神经前体细胞的增殖和存活，在体外和体内调节成年海马神经发生，从而维持神经干细胞池中的细胞分裂和细胞死亡之间的平衡。越来越多的报道表明，神经发生龛中的这些小胶质细胞与非神经发生区的小胶质细胞不同。在这里，我们提供的证据表明海马小胶质细胞表现出转录组异质性，其中一些细胞表达与神经发生相关的基因。通过使用单细胞 RNA 测序对海马中的髓系细胞进行全面分析，我们发现了一小部分但独特的小胶质细胞群体，这些细胞中与稳态小胶质细胞相关的基因减少，与吞噬作用相关的基因富集。有趣的是，这个群体还表达了一个与先前表征的表型具有显著重叠的基因特征，包括与疾病相关的小胶质细胞（DAM），这是一种特别独特和引人注目的小胶质细胞状态。
