Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies

被引：78

作者：

Mair, Barbara ^{[1
]}

Tomic, Jelena ^{[1
]}

Masud, Sanna N. ^{[1
,2
]}

Tonge, Peter ^{[3
]}

Weiss, Alexander ^{[1
]}

Usaj, Matej ^{[1
]}

Tong, Amy Hin Yan ^{[1
]}

Kwan, Jamie J. ^{[4
,5
]}

Brown, Kevin R. ^{[1
]}

Titus, Emily ^{[3
]}

Atkins, Michael ^{[4
,5
,6
]}

Chan, Katherine S. K. ^{[1
]}

Munsie, Lise ^{[3
]}

Habsid, Andrea ^{[1
]}

Han, Hong ^{[1
]}

Kennedy, Marion ^{[4
,5
]}

Cohen, Brenda ^{[4
,5
]}

Keller, Gordon ^{[4
,5
,6
]}

Moffat, Jason ^{[1
,2
,7
,8
]}

机构：

[1] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada

[2] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[3] Ctr Commercializat Regenerat Med, Toronto, ON, Canada

[4] Univ Toronto, Univ Hlth Network, McEwen Stem Cell Inst, Toronto, ON, Canada

[5] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[6] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[7] Canadian Inst Adv Res, Toronto, ON, Canada

[8] Univ Toronto, Inst Biomat & BioMed Engn, Toronto, ON, Canada

来源：

CELL REPORTS | 2019年 / 27卷 / 02期

关键词：

SET ENRICHMENT ANALYSIS; WIDE RNAI SCREEN; HEMATOPOIETIC PROGENITORS; EXPRESSION; DIFFERENTIATION; REVEALS; VISUALIZATION; DATABASE; PLATFORM; FATE;

D O I：

10.1016/j.celrep.2019.02.041

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging essential genes (EGs) that are indispensable for hPSC fitness, defined as cell reproduction in this study. To map essential genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify EGs. Among these, we found FOXH1 and VENTX, genes that encode transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. hPSC EGs are substantially different from other human model cell lines, and EGs in hPSCs are highly context dependent with respect to different growth substrates. Our CRISPR screens establish parameters for genome-wide screens in hPSCs, which will facilitate the characterization of unappreciated genetic regulators of hPSC biology.

引用

页码：599 / +

页数：29

共 74 条

[1]

[Anonymous], 2016, bioRxiv, DOI [10.1101/060012, DOI 10.1101/060012]

[2] Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs [J].

Bertero, Alessandro ;

Pawlowski, Matthias ;

Ortmann, Daniel ;

Snijders, Kirsten ;

Yiangou, Loukia ;

de Brito, Miguel Cardoso ;

Brown, Stephanie ;

Bernard, William G. ;

Cooper, James D. ;

Giacomelli, Elisa ;

Gambardella, Laure ;

Hannan, Nicholas R. F. ;

Iyer, Dharini ;

Sampaziotis, Fotios ;

Serrano, Felipe ;

Zonneveld, Marielle C. F. ;

Sinha, Sanjay ;

Kotter, Mark ;

Vallier, Ludovic .

DEVELOPMENT, 2016, 143 (23) :4405-4418

[3] Switch Enhancers Interpret TGF-β and Hippo Signaling to Control Cell Fate in Human Embryonic Stem Cells [J].

Beyer, Tobias A. ;

Weiss, Alexander ;

Khomchuk, Yuliya ;

Huang, Kui ;

Ogunjimi, Abiodun A. ;

Varelas, Xaralabos ;

Wrana, Jeffrey L. .

CELL REPORTS, 2013, 5 (06) :1611-1624

[4] Gene essentiality and synthetic lethality in haploid human cells [J].

Blomen, Vincent A. ;

Majek, Peter ;

Jae, Lucas T. ;

Bigenzahn, Johannes W. ;

Nieuwenhuis, Joppe ;

Staring, Jacqueline ;

Sacco, Roberto ;

van Diemen, Ferdy R. ;

Olk, Nadine ;

Stukalov, Alexey ;

Marceau, Caleb ;

Janssen, Hans ;

Carette, Jan E. ;

Bennett, Keiryn L. ;

Colinge, Jacques ;

Superti-Furga, Giulio ;

Brummelkamp, Thijn R. .

SCIENCE, 2015, 350 (6264) :1092-1096

[5] Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia [J].

Boerkoel, CF ;

Takashima, H ;

John, J ;

Yan, J ;

Stankiewicz, P ;

Rosenbarker, L ;

André, JL ;

Bogdanovic, R ;

Burguet, A ;

Cockfield, S ;

Cordeiro, I ;

Fründ, S ;

Illies, F ;

Joseph, M ;

Kaitila, I ;

Lama, G ;

Loirat, C ;

McLeod, DR ;

Milford, DV ;

Petty, EM ;

Rodrigo, F ;

Saraiva, JM ;

Schmidt, B ;

Smith, GC ;

Spranger, J ;

Stein, A ;

Thiele, H ;

Tizard, J ;

Weksberg, R ;

Lupski, JR ;

Stockton, DW .

NATURE GENETICS, 2002, 30 (02) :215-220

[6] Setd1b, encoding a histone 3 lysine 4 methyltransferase, is a maternal effect gene required for the oogenic gene expression program [J].

Brici, David ;

Zhang, Qinyu ;

Reinhardt, Susanne ;

Dahl, Andreas ;

Hartmann, Hella ;

Schmidt, Kerstin ;

Goveas, Neha ;

Huang, Jiahao ;

Gahurova, Lenka ;

Kelsey, Gavin ;

Anastassiadis, Konstantinos ;

Stewart, A. Francis ;

Kranz, Andrea .

DEVELOPMENT, 2017, 144 (14) :2806-2817

[7] Easy quantitative assessment of genome editing by sequence trace decomposition [J].

Brinkman, Eva K. ;

Chen, Tao ;

Amendola, Mario ;

van Steensel, Bas .

NUCLEIC ACIDS RESEARCH, 2014, 42 (22)

[8] Microcephalin coordinates mitosis in the syncytial Drosophila embryo [J].

Brunk, Kathrin ;

Vernay, Bertrand ;

Griffith, Elen ;

Reynolds, Natalie L. ;

Strutt, David ;

Ingham, Philip W. ;

Jackson, Andrew P. .

JOURNAL OF CELL SCIENCE, 2007, 120 (20) :3578-3588

[9] OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines [J].

Chen, Wei-Hua ;

Lu, Guanting ;

Chen, Xiao ;

Zhao, Xing-Ming ;

Bork, Peer .

NUCLEIC ACIDS RESEARCH, 2017, 45 (D1) :D940-D944

[10] Engineering Human Stem Cell Lines with Inducible Gene Knockout using CRISPR/Cas9 [J].

Chen, Yuejun ;

Cao, Jingyuan ;

Xiong, Man ;

Petersen, Andrew J. ;

Dong, Yi ;

Tao, Yunlong ;

Huang, Cindy Tzu-Ling ;

Du, Zhongwei ;

Zhang, Su-Chun .

CELL STEM CELL, 2015, 17 (02) :233-244

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