星形胶质细胞可转化为脑干细胞

来自德国癌症研究中心(DKFZ)和海德堡大学的科学家在《自然》杂志上发表了他们的发现。

Scientists from the German Cancer Research Center (DKFZ) and Heidelberg University have published their findings in the journal Nature.

在小鼠实验中，研究人员发现，实验诱导的脑血流缺乏会通过表观遗传将星形胶质细胞重新编程为脑干细胞，而脑干细胞反过来又会产生神经祖细胞。

In mice, the researchers showed that experimentally induced lack of blood flow in the brain epigenetically reprograms astrocytes into brain stem cells, which in turn can give rise to nerve progenitor cells.

这一发现表明，星形胶质细胞有可能用于再生医学，以取代受损的神经细胞。

This discovery shows that astrocytes could potentially be used in regenerative medicine to replace damaged nerve cells.

由Martin-Villalba和Simon Anders(海德堡大学BioQuant中心)领导的团队从成年小鼠年轻神经元发育的大脑区域之一“脑室-室下区”(vSVZ)中分离出普通星形胶质细胞和脑干细胞。

The teams led by Martin-Villalba and Simon Anders (BioQuant, Center, Heidelberg University) isolated both ordinary astrocytes and brain stem cells from one of the regions of the brain where young neurons develop in adult mice, the "ventricular-subventricular zone" (vSVZ).

在这项研究中，干细胞专家注意到，脑干细胞具有一种特殊的DNA甲基化模式，使它们与其他星形胶质细胞区别开来。

During this study, the stem cell experts noticed that brain stem cells have a special DNA methylation pattern that distinguishes them from other astrocytes.

早期的研究已经表明，血液供应的缺乏，比如发生在脑损伤中，会增加新生神经细胞的数量。

Earlier studies had already shown that a lack of blood supply, such as occurs in brain injuries, increases the number of newborn nerve cells.

甲基化谱的改变在这个过程中起作用吗?

Do altered methylation profiles play a role in this process?

为了研究这一点，研究人员在短时间内中断了鼠大脑的血液供应。

To investigate this, the researchers interrupted the blood supply to the brain of mice for a short time.

结果具有典型干细胞甲基化特征的星形胶质细胞也可以在vSVZ外检测到，并且神经祖细胞的数量也有所增加。

As a result, astrocytes with the typical stem cell methylation profile could be detected even outside the vSVZ, as well as an increased number of nerve progenitor cells.

血流的缺乏显然会导致大脑某些区域的星形胶质细胞重新分配DNA上的甲基标记，从而使启动干细胞程序。

The lack of blood flow apparently causes astrocytes in certain areas of the brain to redistribute the methyl marks on their DNA in such a way that their stem cell program becomes accessible.

Journal References:

1. Lukas P. M. Kremer, Santiago Cerrizuela, Hadil El-Sammak, Mohammad Eid Al Shukairi, Tobias Ellinger, Jannes Straub, Aylin Korkmaz, Katrin Volk, Jan Brunken, Susanne Kleber, Simon Anders, Ana Martin-Villalba. DNA methylation controls stemness of astrocytes in health and ischaemia. Nature, 2024; DOI: 10.1038/s41586-024-07898-9

2. Lukas P. M. Kremer, Martina M. Braun, Svetlana Ovchinnikova, Leonie Küchenhoff, Santiago Cerrizuela, Ana Martin-Villalba, Simon Anders. Analyzing single-cell bisulfite sequencing data with MethSCAn. Nature Methods, 2024; DOI: 10.1038/s41592-024-02347-x