Single-cell epigenome analysis reveals age-associated decay of heterochromatin domains in excitatory neurons in the mouse brain.
Single-cell epigenome analysis reveals age-associated decay of heterochromatin domains in excitatory neurons in the mouse brain.
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DOI：
10.1038/s41422-022-00719-6
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发表时间：
2022-11
期刊：
影响因子：
44.1
通讯作者：
Ren, Bing
中科院分区：
文献类型：
--
作者：
Zhang, Yanxiao;Amaral, Maria Luisa;Zhu, Chenxu;Grieco, Steven Francis;Hou, Xiaomeng;Lin, Lin;Buchanan, Justin;Tong, Liqi;Preissl, Sebastian;Xu, Xiangmin;Ren, Bing
异染色质的丢失被认为是哺乳动物器官功能早衰和年龄相关性下降的原因;然而，受这种表观遗传变化影响的特定细胞类型和基因位点仍然不清楚。为了解决这一知识差距，我们在年轻，中年和老年小鼠的大脑，心脏，骨骼肌和骨髓中以单细胞分辨率探测染色质可及性，并评估了32种主要细胞类型中353，126个候选顺式调节元件（cCREs）的年龄相关变化。出乎意料的是，我们检测到增加的染色质可及性内特定的异染色质结构域在老年小鼠兴奋性神经元。在这些基因组位点的染色质可及性的获得伴随着异染色质的细胞类型特异性损失和LINE 1元件的激活。免疫染色进一步证实了兴奋性神经元中异染色质标记H3 K9 me 3的丢失，但抑制性神经元或神经胶质细胞中则没有。我们的研究结果揭示了老年小鼠染色质景观的细胞类型特异性变化，并揭示了哺乳动物衰老中异染色质丢失的范围。
Loss of heterochromatin has been implicated as a cause of pre-mature aging and age-associated decline in organ functions in mammals; however, the specific cell types and gene loci affected by this type of epigenetic change have remained unclear. To address this knowledge gap, we probed chromatin accessibility at single-cell resolution in the brains, hearts, skeletal muscles, and bone marrows from young, middle-aged, and old mice, and assessed age-associated changes at 353,126 candidate cis-regulatory elements (cCREs) across 32 major cell types. Unexpectedly, we detected increased chromatin accessibility within specific heterochromatin domains in old mouse excitatory neurons. The gain of chromatin accessibility at these genomic loci was accompanied by the cell-type-specific loss of heterochromatin and activation of LINE1 elements. Immunostaining further confirmed the loss of the heterochromatin mark H3K9me3 in the excitatory neurons but not in inhibitory neurons or glial cells. Our results reveal the cell-type-specific changes in chromatin landscapes in old mice and shed light on the scope of heterochromatin loss in mammalian aging.
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DOI：
10.1038/s43587-021-00072-0
发表时间：
2021-07
期刊：
Nature aging
影响因子：
--
作者：
Byrns CN;Saikumar J;Bonini NM
通讯作者：
Bonini NM
影响因子：
16.6
作者：
Angelidis, Ilias;Simon, Lukas M.;Schiller, Herbert B.
通讯作者：
Schiller, Herbert B.
影响因子：
7.8
作者：
Chojnowski, Alexandre;Ong, Peh Fern;Dreesen, Oliver
通讯作者：
Dreesen, Oliver
影响因子：
64.5
作者：
Bonev B;Mendelson Cohen N;Szabo Q;Fritsch L;Papadopoulos GL;Lubling Y;Xu X;Lv X;Hugnot JP;Tanay A;Cavalli G
通讯作者：
Cavalli G
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y