Modulating mesendoderm competence during human germ layer differentiation.
Modulating mesendoderm competence during human germ layer differentiation.
复制标题
DOI：
10.1016/j.celrep.2021.109990
复制
发表时间：
2021-11-09
期刊：
影响因子：
8.8
通讯作者：
Ramanathan S
中科院分区：
文献类型：
--
作者：
Valcourt JR;Huang RE;Kundu S;Venkatasubramanian D;Kingston RE;Ramanathan S
随着多能人类胚胎干细胞向一个胚层命运发展，它们失去了采用替代命运的能力。使用一个低维的反应坐标来监测外胚层的进展，我们表明，一个分化的干细胞的概率，采用适当的信号福尔斯急剧下降的中内胚层的命运在一个点沿着外胚层的轨迹。我们使用该反应坐标来基于细胞的中内胚层能力前瞻性地分离和描绘分化细胞，并分析其RNA测序（RNA-seq）和使用测序（ATAC-seq）谱测定转座酶可接近的染色质，以鉴定控制细胞的中内胚层能力的转录因子。通过调节这些关键转录因子，我们可以扩大或缩小适应窗口，使其沿着外胚层分化轨迹适应中内胚层的命运。潜在的基因调控网络的能力，以调节能力是必不可少的了解人类的发展和控制的命运选择的干细胞在体外。人类胚胎干细胞在沿着外胚层轨迹的特定点上丧失了承担中内胚层命运的能力。Valcourt等人分析了感受态丧失前后细胞群体的转录组学和染色质可及性，以揭示其扰动可以扩大或收缩中内胚层感受态的基因。
As pluripotent human embryonic stem cells progress toward one germ layer fate, they lose the ability to adopt alternative fates. Using a low-dimensional reaction coordinate to monitor progression toward ectoderm, we show that a differentiating stem cell’s probability of adopting a mesendodermal fate given appropriate signals falls sharply at a point along the ectoderm trajectory. We use this reaction coordinate to prospectively isolate and profile differentiating cells based on their mesendoderm competence and analyze their RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles to identify transcription factors that control the cell’s mesendoderm competence. By modulating these key transcription factors, we can expand or contract the window of competence to adopt the mesendodermal fate along the ectodermal differentiation trajectory. The ability of the underlying gene regulatory network to modulate competence is essential for understanding human development and controlling the fate choices of stem cells in vitro. The competence of human embryonic stem cells to take on mesendoderm fates is lost at a particular point along the ectoderm trajectory. Valcourt et al. analyze transcriptomics and chromatin accessibility of cell populations before and after competence loss to reveal genes whose perturbation can expand or contract mesendoderm competence.
登录
查看更多内容
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
9.8
作者：
McQuin C;Goodman A;Chernyshev V;Kamentsky L;Cimini BA;Karhohs KW;Doan M;Ding L;Rafelski SM;Thirstrup D;Wiegraebe W;Singh S;Becker T;Caicedo JC;Carpenter AE
通讯作者：
Carpenter AE
影响因子：
64.5
作者：
Mullen AC;Orlando DA;Newman JJ;Lovén J;Kumar RM;Bilodeau S;Reddy J;Guenther MG;DeKoter RP;Young RA
通讯作者：
Young RA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
64.5
作者：
Loh KM;Chen A;Koh PW;Deng TZ;Sinha R;Tsai JM;Barkal AA;Shen KY;Jain R;Morganti RM;Shyh-Chang N;Fernhoff NB;George BM;Wernig G;Salomon REA;Chen Z;Vogel H;Epstein JA;Kundaje A;Talbot WS;Beachy PA;Ang LT;Weissman IL
通讯作者：
Weissman IL