Pierson Smela Merrick, Adams Jessica, Ma Carl, Breimann Laura, Widocki Ursula, Shioda Toshi, Church George M
Wyss Institute, Harvard University; Boston, 02215, USA.
Department of Genetics, Harvard Medical School; Boston, 02115, USA.
bioRxiv. 2024 May 31:2024.05.31.596483. doi: 10.1101/2024.05.31.596483.
An model of human meiosis would accelerate research into this important reproductive process and development of therapies for infertility. We have developed a method to induce meiosis starting from male or female human pluripotent stem cells. We demonstrate that DNMT1 inhibition, retinoid signaling activation, and overexpression of regulatory factors (anti-apoptotic BCL2, and pro-meiotic HOXB5, BOLL, or MEIOC) rapidly activates meiosis, with leptonema beginning at 6 days, zygonema at 9 days, and pachynema at 12 days. Immunofluorescence microscopy shows key aspects of meiosis, including chromosome synapsis and sex body formation. The meiotic cells express genes similar to meiotic oogonia , including all synaptonemal complex components and machinery for meiotic recombination. These findings establish an accessible system for inducing human meiosis .
人类减数分裂模型将加速对这一重要生殖过程的研究以及不育症治疗方法的开发。我们已经开发出一种从人类多能干细胞诱导减数分裂的方法。我们证明，抑制DNA甲基转移酶1、激活视黄酸信号以及过表达调控因子（抗凋亡的BCL2以及促减数分裂的HOXB5、BOLL或MEIOC）可迅速激活减数分裂，细线期在第6天开始，偶线期在第9天开始，粗线期在第12天开始。免疫荧光显微镜检查显示了减数分裂的关键方面，包括染色体联会和性体形成。减数分裂细胞表达的基因与减数分裂期卵原细胞相似，包括所有联会复合体成分和减数分裂重组机制。这些发现建立了一个可诱导人类减数分裂的系统。
