Kerimoglu Cemil, Pham Linh, Tonchev Anton B, Sakib M Sadman, Xie Yuanbin, Sokpor Godwin, Ulmke Pauline Antonie, Kaurani Lalit, Abbas Eman, Nguyen Huong, Rosenbusch Joachim, Michurina Alexandra, Capece Vincenzo, Angelova Meglena, Maricic Nenad, Brand-Saberi Beate, Esgleas Miriam, Albert Mareike, Minkov Radoslav, Kovachev Emil, Teichmann Ulrike, Seong Rho H, Huttner Wieland B, Nguyen Huu Phuc, Stoykova Anastassia, Staiger Jochen F, Fischer Andre, Tuoc Tran
German Center for Neurodegenerative Diseases, 37077 Goettingen, Germany.
Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany.
Sci Adv. 2021 Sep 17;7(38):eabc6792. doi: 10.1126/sciadv.abc6792. Epub 2021 Sep 15.
Increase in the size of human neocortex―acquired in evolution―accounts for the unique cognitive capacity of humans. This expansion reflects the evolutionarily enhanced proliferative ability of basal progenitors (BPs), including the basal radial glia and basal intermediate progenitors (bIPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, how the epigenome in BPs differs across species is not known. Here, we report that histone H3 acetylation is a key epigenetic regulation in bIP amplification and cortical expansion. Through epigenetic profiling of sorted bIPs, we show that histone H3 lysine 9 acetylation (H3K9ac) is low in murine bIPs and high in human bIPs. Elevated H3K9ac preferentially increases bIP proliferation, increasing the size and folding of the normally smooth mouse neocortex. H3K9ac drives bIP amplification by increasing expression of the evolutionarily regulated gene, , in developing cortex. Our findings demonstrate a previously unknown mechanism that controls cortical architecture.
人类新皮质尺寸的增加——在进化过程中获得——解释了人类独特的认知能力。这种扩张反映了基底祖细胞（BPs）增殖能力在进化上的增强，包括哺乳动物皮质中的基底放射状胶质细胞和基底中间祖细胞（bIPs），这可能是通过BPs中的表观遗传改变获得的。然而，不同物种的BPs表观基因组如何不同尚不清楚。在这里，我们报告组蛋白H3乙酰化是bIP扩增和皮质扩张中的关键表观遗传调控。通过对分选的bIPs进行表观遗传分析，我们发现组蛋白H3赖氨酸9乙酰化（H3K9ac）在小鼠bIPs中较低，而在人类bIPs中较高。升高的H3K9ac优先增加bIP增殖，增加正常光滑的小鼠新皮质的大小和折叠。H3K9ac通过增加发育中的皮质中进化调控基因的表达来驱动bIP扩增。我们的发现证明了一种以前未知的控制皮质结构的机制。
