Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina.
Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina.
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DOI：
10.1016/j.celrep.2021.109994
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发表时间：
2021-11-16
期刊：
影响因子：
8.8
通讯作者：
Blackshaw S
中科院分区：
文献类型：
--
作者：
Lyu P;Hoang T;Santiago CP;Thomas ED;Timms AE;Appel H;Gimmen M;Le N;Jiang L;Kim DW;Chen S;Espinoza DF;Telger AE;Weir K;Clark BS;Cherry TJ;Qian J;Blackshaw S
由转录因子及其靶位点组成的基因调控网络（GRNs）控制着发育中的中枢神经系统的神经发生和细胞命运。在这项研究中，我们在发育中的小鼠和人类视网膜中使用集成的单细胞RNA和单细胞ATAC测序（scATAC-seq）分析，以识别由细胞类型特异性转录因子组成的多个相互关联的、进化上保守的GRN，这些转录因子既激活基因在它们自己的网络中，又抑制其他网络中的基因。这些GRN控制初级祖细胞的时间模式，调节从初级祖细胞到神经源性祖细胞的转变，并驱动每种主要视网膜细胞类型的特化。我们证实，NFI转录因子选择性地激活基因的表达，促进后期的时间特性在初级视网膜祖细胞和确定其他转录因子，调节杆感光细胞的规格在出生后的视网膜。这项研究清点了控制视网膜发育的顺式和反式作用因子，并可以指导旨在取代因疾病而失去的视网膜神经元的基于细胞的治疗。Lyu等人在单细胞水平上使用基因表达和染色质可及性的综合分析，确定了进化上保守的基因调控网络，这些网络调节发育中小鼠和人类视网膜中所有主要细胞类型的时间模式，神经发生和细胞命运特化，并在功能上验证了这些预测。
Gene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis and cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA and single-cell ATAC sequencing (scATAC-seq) analysis in developing mouse and human retina to identify multiple interconnected, evolutionarily conserved GRNs composed of cell-type-specific transcription factors that both activate genes within their own network and inhibit genes in other networks. These GRNs control temporal patterning in primary progenitors, regulate transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirm that NFI transcription factors selectively activate expression of genes promoting late-stage temporal identity in primary retinal progenitors and identify other transcription factors that regulate rod photoreceptor specification in postnatal retina. This study inventories cis- and trans-acting factors that control retinal development and can guide cell-based therapies aimed at replacing retinal neurons lost to disease. Using integrated analysis of gene expression and chromatin accessibility at the single-cell level, Lyu et al. identify evolutionarily conserved gene regulatory networks that regulate temporal patterning, neurogenesis, and cell-fate specification for all major cell types in the developing mouse and human retina and functionally validate these predictions.
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影响因子：
4.6
作者：
Chan, Candace S. Y.;Lonfat, Nicolas;Wang, Sui
通讯作者：
Wang, Sui
在发育，重编程和肿瘤发生过程中，视网膜的动态表观遗传景观。
影响因子：
16.2
作者：
Aldiri I;Xu B;Wang L;Chen X;Hiler D;Griffiths L;Valentine M;Shirinifard A;Thiagarajan S;Sablauer A;Barabas ME;Zhang J;Johnson D;Frase S;Zhou X;Easton J;Zhang J;Mardis ER;Wilson RK;Downing JR;Dyer MA;St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project
通讯作者：
St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project
影响因子：
2.7
作者：
Forbes-Osborne MA;Wilson SG;Morris AC
通讯作者：
Morris AC
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cowan CS;Renner M;De Gennaro M;Gross-Scherf B;Goldblum D;Hou Y;Munz M;Rodrigues TM;Krol J;Szikra T;Cuttat R;Waldt A;Papasaikas P;Diggelmann R;Patino-Alvarez CP;Galliker P;Spirig SE;Pavlinic D;Gerber-Hollbach N;Schuierer S;Srdanovic A;Balogh M;Panero R;Kusnyerik A;Szabo A;Stadler MB;Orgül S;Picelli S;Hasler PW;Hierlemann A;Scholl HPN;Roma G;Nigsch F;Roska B
通讯作者：
Roska B