小柯机器人

人类肾脏类器官的全基因组筛选可揭示肾脏的发育和疾病发生
2021-11-30 15:55

近日,瑞士诺华生物医学研究所Philipp S. Hoppe及其小组利用人类肾脏类器官的全基因组筛选揭示肾脏的发育和疾病发生。2021年11月29日,《细胞—干细胞》杂志在线发表了这项成果。

研究人员展示了诱导多能干细胞(iPSC)来源的肾脏器官中的全基因组CRISPR筛选。诱导性基因组编辑、纵向取样以及肾小管和基质细胞的终点分类相结合,产生了一个复杂的、高质量的数据集,并揭示了从早期发育到"成年"上皮形态发生的广泛认知。这个功能数据集可以通过ROCK的抑制来改善中胚层的诱导,包含了单基因和复杂性状的肾脏疾病基因,确认了另外两个先天性肾脏和尿路异常(CAKUT)基因(CCDC170和MYH7B),并提供了一个庞大的纤毛症相关基因的候选名单。

最后,对Jagged1控制上皮细胞增殖的顺式抑制作用的鉴定表明,在汇集CRISPR筛选中的镶嵌式敲除可以揭示复杂组织中异质细胞群之间的交流方式。这些数据是肾脏研究界的丰富资源,也是未来iPSC衍生器官CRISPR筛选的基准。

据了解,人类器官能用于研究增殖、系谱分化和三维组织发育。

附:英文原文

Title: Genome-wide screening in human kidney organoids identifies developmental and disease-related aspects of nephrogenesis

Author: Rosemarie Ungricht, Laure Guibbal, Marie-Christine Lasbennes, Vanessa Orsini, Martin Beibel, Annick Waldt, Rachel Cuttat, Walter Carbone, Anne Basler, Guglielmo Roma, Florian Nigsch, Jan S. Tchorz, Dominic Hoepfner, Philipp S. Hoppe

Issue&Volume: 2021-11-29

Abstract: Human organoids allow the study of proliferation, lineage specification, and 3D tissuedevelopment. Here we present a genome-wide CRISPR screen in induced pluripotent stemcell (iPSC)-derived kidney organoids. The combination of inducible genome editing,longitudinal sampling, and endpoint sorting of tubular and stromal cells generateda complex, high-quality dataset uncovering a broad spectrum of insightful biologyfrom early development to “adult” epithelial morphogenesis. Our functional dataset allowsimproving mesoderm induction by ROCK inhibition, contains monogenetic and complextrait kidney disease genes, confirms two additional congenital anomalies of the kidneyand urinary tract (CAKUT) genes (CCDC170 and MYH7B), and provides a large candidatelist of ciliopathy-related genes. Finally, identification of a cis-inhibitory effect of Jagged1 controlling epithelial proliferation shows how mosaicknockouts in pooled CRISPR screening can reveal ways of communication between heterogeneouscell populations in complex tissues. These data serve as a rich resource for the kidneyresearch community and as a benchmark for future iPSC-derived organoid CRISPR screens.

DOI: 10.1016/j.stem.2021.11.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00449-5

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章:《细胞—干细胞》:Online/在线发表

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