A reference induced pluripotent stem cell line for large-scale collaborative studies
Authors: Pantazis Caroline B. , Yang Andrian , Lara Erika , McDonough Justin A. , Blauwendraat Cornelis , Peng Lirong , Oguro Hideyuki , Kanaujiya Jitendra , Zou Jizhong , Sebesta David , Pratt Gretchen , Cross Erin , Blockwick Jeffrey , Buxton Philip , Kinner-Bibeau Lauren , Medura Constance , Tompkins Christopher , Hughes Stephen , Santiana Marianita , Faghri Faraz , Nalls Mike A. , Vitale Daniel , Ballard Shannon , Qi Yue A. , Ramos Daniel M. , Anderson Kailyn M. , Stadler Julia , Narayan Priyanka , Papademetriou Jason , Reilly Luke , Nelson Matthew P. , Aggarwal Sanya , Rosen Leah U. , Kirwan Peter , Pisupati Venkat , Coon Steven L. , Scholz Sonja W. , Priebe Theresa , Öttl Miriam , Dong Jian , Meijer Marieke , Janssen Lara J.M. , Lourenco Vanessa S. , van der Kant Rik , Crusius Dennis , Paquet Dominik , Raulin Ana-Caroline , Bu Guojun , Held Aaron , Wainger Brian J. , Gabriele Rebecca M.C. , Casey Jackie M , Wray Selina , Abu-Bonsrah Dad , Parish Clare L. , Beccari Melinda S. , Cleveland Don W. , Li Emmy , Rose Indigo V.L. , Kampmann Martin , Aristoy Carles Calatayud , Verstreken Patrik , Heinrich Laurin , Chen Max Y. , Schüle Birgitt , Dou Dan , Holzbaur Erika L.F. , Zanellati Maria Clara , Basundra Richa , Deshmukh Mohanish , Cohen Sarah , Khanna Richa , Raman Malavika , Nevin Zachary S. , Matia Madeline , Lent Jonas Van , Timmerman Vincent , Conklin Bruce R. , Chase Katherine Johnson , Zhang Ke , Funes Salome , Bosco Daryl A. , Erlebach Lena , Welzer Marc , Kronenberg-Versteeg Deborah , Lyu Guochang , Arenas Ernest , Coccia Elena , Sarrafha Lily , Ahfeldt Tim , Marioni John C. , Skarnes William C. , Cookson Mark R. , Ward Michael E. , Merkle Florian T. 
Published: December 2021

AbstractHuman induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate iPSC lines and deeply characterised their genetic properties using whole genome sequencing, their genomic stability upon CRISPR/Cas9-based gene editing, and their phenotypic properties including differentiation to commonly-used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and hundreds of its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.SummaryThe authors of this collaborative study deeply characterized human induced pluripotent stem cell (iPSC) lines to rationally select a clonally-derived cell line that performs well across multiple modalities. KOLF2.1J was identified as a candidate reference cell line based on single-cell analysis of its gene expression in the pluripotent state, whole genome sequencing, genomic stability after highly efficient CRISPR-mediated gene editing, integrity of the p53 pathway, and the efficiency with which it differentiated into multiple target cell populations. Since it is deeply characterized and can be readily acquired, KOLF2.1J is an attractive reference cell line for groups working with iPSCs.Graphical abstract