Single-nucleus characterization of adult mouse spinal dynorphin-lineage cells and identification of persistent transcriptional effects of neonatal hindpaw incision.
Single-nucleus characterization of adult mouse spinal dynorphin-lineage cells and identification of persistent transcriptional effects of neonatal hindpaw incision.
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成年小鼠脊椎旋球细胞的单核表征以及鉴定新生儿后爪切口的持续转录作用。
DOI：
10.1097/j.pain.0000000000002007
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发表时间：
2021-01
期刊：
影响因子：
7.4
通讯作者：
Baccei ML
中科院分区：
文献类型：
--
作者：
Serafin EK;Paranjpe A;Brewer CL;Baccei ML
新生儿组织损伤可对中枢神经系统的伤害性处理产生长期影响，这可能反映了脊髓背角突触抑制和兴奋之间的正常平衡的持续性损伤诱发的改变。脊髓强啡肽谱系（pDyn）神经元是抑制回路的一部分，该抑制回路限制伤害性输入流到大脑并且被新生儿组织损伤破坏。为了确定这种破坏的潜在分子基础，对成年小鼠脊髓pDyn细胞进行了无偏单核RNAseq分析，深入表征了该群体，然后确定了新生儿后爪切口引起的基因表达变化。分析显示11个转录不同的亚群（即集群）的强啡肽谱系细胞，包括抑制性和兴奋性神经元。损伤诱发的差异基因表达的调查确定了15个基因，显着上调或下调的成年pDyn神经元与幼稚的同窝对照组相比，与集群特异性和泛神经元的转录变化观察。几个已鉴定的基因，如Oxr1和Fth1（编码铁蛋白），与细胞应激反应有关。然而，相对较低数量的损伤诱发的差异表达基因也表明，转录后调节pDyn神经元内可能发挥了关键作用，在启动开发伤害性回路的早期生命损伤。总的来说，这些发现揭示了对背角中间神经元的关键群体的分子异质性的新见解，该群体先前与机械性疼痛和瘙痒的抑制有关。
Neonatal tissue damage can have long-lasting effects on nociceptive processing in the central nervous system, which may reflect persistent injury-evoked alterations to the normal balance between synaptic inhibition and excitation in the spinal dorsal horn. Spinal dynorphin-lineage (pDyn) neurons are part of an inhibitory circuit which limits the flow of nociceptive input to the brain and is disrupted by neonatal tissue damage. To identify the potential molecular underpinnings of this disruption, an unbiased single-nucleus RNAseq analysis of adult mouse spinal pDyn cells characterized this population in depth and then identified changes in gene expression evoked by neonatal hindpaw incision. The analysis revealed 11 transcriptionally distinct subpopulations (ie, clusters) of dynorphin-lineage cells, including both inhibitory and excitatory neurons. Investigation of injury-evoked differential gene expression identified 15 genes that were significantly upregulated or downregulated in adult pDyn neurons from neonatally incised mice compared with naive littermate controls, with both cluster-specific and pan-neuronal transcriptional changes observed. Several of the identified genes, such as Oxr1 and Fth1 (encoding ferritin), were related to the cellular stress response. However, the relatively low number of injury-evoked differentially expressed genes also suggests that posttranscriptional regulation within pDyn neurons may play a key role in the priming of developing nociceptive circuits by early-life injury. Overall, the findings reveal novel insights into the molecular heterogeneity of a key population of dorsal horn interneurons that has previously been implicated in the suppression of mechanical pain and itch.
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影响因子：
7.4
作者：
Cameron D;Polgár E;Gutierrez-Mecinas M;Gomez-Lima M;Watanabe M;Todd AJ
通讯作者：
Todd AJ
DOI：
10.1126/science.aac8653
发表时间：
2015-10-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bourane S;Duan B;Koch SC;Dalet A;Britz O;Garcia-Campmany L;Kim E;Cheng L;Ghosh A;Ma Q;Goulding M
通讯作者：
Goulding M
影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
3.5
作者：
Bianchi, Marzia;Giacomini, Elisa;Magnani, Mauro
通讯作者：
Magnani, Mauro
影响因子：
25
作者：
Ferrini F;Trang T;Mattioli TA;Laffray S;Del'Guidice T;Lorenzo LE;Castonguay A;Doyon N;Zhang W;Godin AG;Mohr D;Beggs S;Vandal K;Beaulieu JM;Cahill CM;Salter MW;De Koninck Y
通讯作者：
De Koninck Y