Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.
Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.
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单细胞分辨率下人视网膜及其器质的细胞类型。
DOI：
10.1016/j.cell.2020.08.013
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发表时间：
2020-09-17
期刊：
影响因子：
64.5
通讯作者：
Roska B
中科院分区：
文献类型：
--
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
人类类器官再现了其靶器官的细胞类型多样性和功能，对于基础和转化研究具有价值。我们开发了具有多个核和突触层以及功能性突触的光敏人类视网膜类器官。我们在7个发育时间点对来自这些类器官的285，441个单细胞以及来自光响应成年人视网膜的外周、中央凹、色素上皮和脉络膜的RNA进行了测序，并进行了组织化学。类器官中的细胞类型在体外成熟为稳定的“发育”状态，其速率与体内人类视网膜发育相似。类器官细胞类型的转录组向成人外周视网膜细胞类型的转录组会聚。在成人视网膜中，疾病相关基因的表达是细胞类型特异性的，并且在类器官中保留了细胞类型特异性。我们在黄斑变性等疾病中发现了意想不到的细胞类型。该资源确定了用于研究类器官疾病机制和人类视网膜靶向修复的细胞靶点。具有功能性突触的光敏多层人视网膜类器官285，441个来自光响应人视网膜和视网膜类器官的转录组类器官细胞类型汇聚成成人外周视网膜细胞类型将视网膜疾病与人视网膜和视网膜类器官细胞类型联系起来光敏，开发了具有功能性突触的多层人视网膜类器官，并以在保留视网膜完整性
Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable “developed” state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas. Light-sensitive, multilayered human retinal organoids with functional synapses 285,441 transcriptomes from light-responsive human retinas and retinal organoids Organoid cell types converge to adult peripheral retinal cell types Linking retinal diseases to human retinal and retinal organoid cell types Light-sensitive, multilayered human retinal organoids with functional synapses are developed and benchmarked against human retinas obtained under conditions that preserve retinal integrity.
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人类诱导的多能干细胞产生具有可变和养分依赖性效率的光响应性视网膜器官。
DOI：
10.1002/stem.2883
发表时间：
2018-10
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Hallam D;Hilgen G;Dorgau B;Zhu L;Yu M;Bojic S;Hewitt P;Schmitt M;Uteng M;Kustermann S;Steel D;Nicholds M;Thomas R;Treumann A;Porter A;Sernagor E;Armstrong L;Lako M
通讯作者：
Lako M
影响因子：
11.1
作者：
Cronin T;Vandenberghe LH;Hantz P;Juttner J;Reimann A;Kacsó AE;Huckfeldt RM;Busskamp V;Kohler H;Lagali PS;Roska B;Bennett J
通讯作者：
Bennett J
影响因子：
25
作者：
Chan KY;Jang MJ;Yoo BB;Greenbaum A;Ravi N;Wu WL;Sánchez-Guardado L;Lois C;Mazmanian SK;Deverman BE;Gradinaru V
通讯作者：
Gradinaru V
影响因子：
11.8
作者：
da Silva S;Cepko CL
通讯作者：
Cepko CL
影响因子：
7.7
作者：
Hsiang JC;Johnson KP;Madisen L;Zeng H;Kerschensteiner D
通讯作者：
Kerschensteiner D