Sibling chimerism among microglia in marmosets.
Sibling chimerism among microglia in marmosets.
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狨猴小胶质细胞中的兄弟嵌合现象。
DOI：
10.1101/2023.10.16.562516
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
McCarroll,StevenA
中科院分区：
文献类型：
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作者：
DelRosario,RicardoCH;Krienen,FennaM;Zhang,Qiangge;Goldman,Melissa;Mello,Curtis;Lutservitz,Alyssa;Ichihara,Kiku;Wysoker,Alec;Nemesh,James;Feng,Guoping;McCarroll,StevenA
嵌合体在大多数哺乳动物中很少发生，但在绒猴和罗望子中很常见，这是双胞胎或三胞胎出生模式的结果，在子宫连接的循环系统(干细胞通过这些循环系统)导致终生持续的血液嵌合体(12%-80%)。雌性绒猴其他器官中Y染色体DNA序列的存在早就表明嵌合体可能也会影响这些器官。然而，一个长期存在的问题是，这种嵌合体是由血液来源的细胞驱动的，还是涉及其他类型的细胞的贡献。为了解决这个问题，我们分析了来自血液、肝脏、肾脏和许多绒猴大脑多个区域的单细胞RNA-SEQ数据，使用转录的单核苷酸多态(SNPs)来识别这些组织中不同类型的细胞中具有兄弟姐妹基因组的细胞。所有组织中的兄弟姐妹来源的嵌合体完全来自造血细胞(即髓系和淋巴系)。在脑组织中，这反映为小胶质细胞(20%-52%)和巨噬细胞(18%-%)之间的兄弟姐妹来源的嵌合体，但在其他常驻细胞类型(即神经元、神经胶质细胞或室管膜细胞)中不存在。来自兄弟姐妹的小胶质细胞的百分比在不同的大脑区域显示出显著的差异，甚至在个体动物中也是如此，这可能反映了兄弟姐妹的小胶质细胞对局部招募或增殖线索的不同反应，或者可能反映了不同脑区不同的克隆性扩张史。在我们分析的动物和组织中，小胶质细胞基因表达谱与当地/宿主环境的关系比与兄弟姐妹遗传差异的关系要强得多。自然发生的绒猴嵌合体将为了解基因、突变和脑环境对小胶质细胞生物学的影响以及区分小胶质细胞和其他细胞类型对脑表型的影响提供新的途径。
Chimerism happens rarely among most mammals but is common in marmosets and tamarins, a result of fraternal twin or triplet birth patterns in which in utero connected circulatory systems (through which stem cells transit) lead to persistent blood chimerism (12–80%) throughout life. The presence of Y-chromosome DNA sequences in other organs of female marmosets has long suggested that chimerism might also affect these organs. However, a longstanding question is whether this chimerism is driven by blood-derived cells or involves contributions from other cell types. To address this question, we analyzed single-cell RNA-seq data from blood, liver, kidney and multiple brain regions across a number of marmosets, using transcribed single nucleotide polymorphisms (SNPs) to identify cells with the sibling’s genome in various cell types within these tissues. Sibling-derived chimerism in all tissues arose entirely from cells of hematopoietic origin (i.e., myeloid and lymphoid lineages). In brain tissue this was reflected as sibling-derived chimerism among microglia (20–52%) and macrophages (18–64%) but not among other resident cell types (i.e., neurons, glia or ependymal cells). The percentage of microglia that were sibling-derived showed significant variation across brain regions, even within individual animals, likely reflecting distinct responses by siblings’ microglia to local recruitment or proliferation cues or, potentially, distinct clonal expansion histories in different brain areas. In the animals and tissues we analyzed, microglial gene expression profiles bore a much stronger relationship to local/host context than to sibling genetic differences. Naturally occurring marmoset chimerism will provide new ways to understand the effects of genes, mutations and brain contexts on microglial biology and to distinguish between effects of microglia and other cell types on brain phenotypes.