新京報訊(記者李麗霞)近日,南開大學生命科學學院、藥物化學生物學國家重點實驗室劉林教授團隊通過完全化學小分子的方法成功將卵巢顆粒細胞重編程為具有生殖系轉移能力的誘導性多能干細胞,進而分化為卵子,并通過正常受精獲得了健康小鼠。該突破屬世界首次,為保持生育能力、調節機體內分泌等研究開辟了新思路。

The team of Professor Liu Lin, School of Life Sciences and State Key Laboratory of Pharmaceutical Chemistry and Biology of Nankai University, has successfully reprogrammed ovarian granulosa cells into inducible pluripotent stem cells with the ability to transfer germ lines, and then differentiated into eggs. This breakthrough is the first time in the world, which opens up new ideas for maintaining fertility and regulating endocrine system.

  卵子是孕育生命的關鍵,卵巢衰老最主要的表征即為卵子的數量和質量急劇下降。如果能夠從體外獲得足夠量的卵子補充到體內的卵巢中,將會對恢復生殖能力并在臨床上治療生殖衰老等疾病具有重要價值。劉林教授團隊利用完全化學小分子的重編程方法解決了這一問題。

Eggs are the key to life, and the most important representation of ovarian aging is the sharp decline in the quantity and quality of eggs. If enough eggs can be obtained from in vitro to replenish the ovaries in vivo, it will be of great value for restoring reproductive capacity and treating diseases such as reproductive aging clinically. Professor Liu Lin's team solved the problem by using the reprogramming of completely chemical small molecules.

  據悉,卵巢顆粒細胞(Granulosacells,GCs)是卵泡中與卵母細胞相互作用并促進卵子發生的一類體細胞,從卵子產生開始,顆粒細胞就一直陪伴在卵子的左右,支持卵子的生長和發育,最早被成功應用于克隆動物的研究。臨床上,卵巢顆粒細胞一般作為體外受精的副產物而被丟棄。

ovarian granulosa cells (gcs) are known to be a class of somatic cells in follicles that interact with oocytes and promote oogenesis. from the beginning of egg production, granulosa cells have been accompanied around the egg, supporting the growth and development of the egg, and were first successfully applied to the study of cloned animals. clinically, ovary granulosa cells are generally discarded as by-products of in vitro fertilization.

  “每個卵子周圍都有數千個顆粒細胞,若能將其誘導為多能細胞并轉換為卵母細胞,就能解決卵子數量匱乏的問題!眲⒘终f。

“Each egg is surrounded by thousands of granulosa cells, which can be induced into pluripotent cells and converted into oocytes to address the shortage of eggs. said Liu Lin.

  帶著這一設想,劉林團隊反復試驗,最終調制了一種含有巴豆酸鈉等化學物質的小分子培養液處理細胞。這種方法能夠將卵巢顆粒細胞高效地轉變為誘導性多能干細胞,并且這些細胞被證明具有穩定的基因組、逐漸延長的端粒和較高的質量。

With this idea in mind, Liu Lin's team experimented repeatedly and eventually modulated a small molecular medium containing chemicals such as sodium croton to process cells. this approach is able to efficiently transform ovarian granulosa cells into induced pluripotent stem cells, and these cells have been shown to have stable genomes, extended telomeres, and higher quality.

  此外,通過另一種含有維生素C等化學物質的小分子培養液支持卵泡的組裝和卵子的發育,能夠使得顆粒細胞來源的多能干細胞成功進入減數分裂,并分化形成卵子。這些卵子也具有穩定的基因組,并能夠進一步形成健康正常的小鼠后代。

in addition, through another small molecular medium containing chemicals such as vitamin c to support follicle assembly and egg development, it can enable granulosa cell-derived pluripotent stem cells to successfully enter meiosis and differentiate into eggs. these eggs also have stable genomes and are able to further form healthy normal mouse offspring.

  日前,介紹該成果的論文發表于國際學術刊物《細胞報告》(CellReports)上,國際頂級刊物《細胞》(Cell)將此發現作為頭條文章推薦。

The findings were published in the international academic journal Cell Reports, which recommended the findings as a headline article.

  劉林團隊博士生、論文第一作者田成磊對新京報記者表示,這一研究要從應用于小鼠到應用于人類還有很長的路要走,因為人類多能干細胞很難分化形成生殖細胞。此外,獲得生殖細胞要用胚胎性腺的體細胞支持生殖細胞發育,小鼠的胚胎性腺體細胞易獲得,從倫理道德考慮,人類的胚胎性腺體細胞很難獲得,因此需要研究新方法從體外誘導分化形成類似于人胚胎性腺體細胞的細胞用于支持生殖細胞的發育。

Tian chenglei, ph.d. student and first author of the thesis, told beijing news that the study had a long way to go from being applied to mice to being applied to humans because it was difficult for human pluripotent stem cells to differentiate into germ cells. In addition, the acquisition of germ cells to support the development of germ cells with somatic cells of embryonic glands, mouse embryonic gland cells are easy to obtain, ethical considerations, human embryonic gland cells are difficult to obtain, so new methods need to be studied to induce differentiation from in vitro to form cells similar to human embryonic gland cells to support the development of germ cells.

  在他看來,與治療不孕不育相比,這項技術在保持生育能力和內分泌功能方面有更廣闊的前景。他談到,治療不孕不育的群體主要集中為年輕人群體,隨著年齡增長,人們對生育能力的需求降低,但是對絕經期(更年期)后卵巢激素分泌不足引起的相關疾病的預防和治療有更多的需求!拔覀冞\用技術從體外獲得足夠量的卵子補充到小鼠體內的卵巢中后發現可以恢復正常的內分泌水平。因此,如果該技術能夠運用到人體,便可以在人體衰老時通過重建卵巢,讓人體擁有年輕化的內分泌功能水平,從而預防和治療相關疾病!

In his view, compared with the treatment of infertility, the technology has a broader prospect of maintaining fertility and endocrine function. He said that the treatment of infertile people mainly focus on the young group, with age, people's demand for fertility is reduced, but there is a greater need for prevention and treatment of related diseases caused by insufficient secretion of ovarian hormones after menopause (menopause). \"We used technology to get enough eggs in vitro to replenish the ovaries in mice and found that normal levels of endocrine can be restored. Therefore, if the technology can be applied to the human body, it can prevent and treat related diseases by reconstructing the ovary and giving the body a younger level of endocrine function.


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