Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors.
Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors.
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DOI：
10.1242/dev.200413
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发表时间：
2022-10-01
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影响因子：
--
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海马体与大脑的基本功能有关，如学习和记忆。与非人类猿类相比，人类海马体的体积明显大于预期，这表明最近的扩张。中间祖细胞，这是能够经历多轮的增殖分裂之前，最终的神经原性分裂，可能发挥了作用，在进化海马扩张。为了研究支持猿海马神经发生的基因调控网络的进化，我们利用人类和黑猩猩诱导的多能干细胞分化为TBR 2（或EOMES）阳性海马中间祖细胞（hpIPC）。我们发现，hpIPC中活跃的基因网络在人类和黑猩猩之间存在显着差异，有大约2500个基因差异表达。我们证明了物种特异性转座子衍生的增强子有助于这些转录组学差异。年轻的转座子，主要是内源性逆转录病毒和SINE-Vntr-Alus（SVA），以物种特异性方式被增选为增强子。人类特异性SVA为数千个新的TBR 2结合位点提供了底物，CRISPR介导的对这些SVA的抑制减弱了人类中间祖细胞中相对于黑猩猩中相同细胞群上调的约25%基因的表达。 人类和黑猩猩海马发育的进化是由年轻的反转录转座子共同选择成为物种特异性增强子介导的。
The hippocampus is associated with essential brain functions, such as learning and memory. Human hippocampal volume is significantly greater than expected compared with that of non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced pluripotent stem cells into TBR2 (or EOMES)-positive hippocampal intermediate progenitor cells (hpIPCs). We found that the gene networks active in hpIPCs are significantly different between humans and chimpanzees, with ∼2500 genes being differentially expressed. We demonstrate that species-specific transposon-derived enhancers contribute to these transcriptomic differences. Young transposons, predominantly endogenous retroviruses and SINE-Vntr-Alus (SVAs), were co-opted as enhancers in a species-specific manner. Human-specific SVAs provided substrates for thousands of novel TBR2-binding sites, and CRISPR-mediated repression of these SVAs attenuated the expression of ∼25% of the genes that are upregulated in human intermediate progenitors relative to the same cell population in the chimpanzee. Evolution of human and chimpanzee hippocampal development was mediated by the co-option of young retrotransposons into species-specific enhancers.
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DOI：
10.1126/science.abc6405
发表时间：
2021-02-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cosby RL;Judd J;Zhang R;Zhong A;Garry N;Pritham EJ;Feschotte C
通讯作者：
Feschotte C
影响因子：
7
作者：
del Rosario RC;Rayan NA;Prabhakar S
通讯作者：
Prabhakar S
影响因子：
3.5
作者：
Datson, N. A.;Morsink, M. C.;de Kloet, E. R.
通讯作者：
de Kloet, E. R.
影响因子：
2.7
作者：
Bekinschtein, Pedro;Katche, Cynthia;Medina, Jorge H.
通讯作者：
Medina, Jorge H.
影响因子：
10.5
作者：
Arnold, Sebastian J.;Huang, Guo-Jen;Groszer, Matthias
通讯作者：
Groszer, Matthias