@article{2d90e5e3ae7349fbbfb35864b7bd5612,
title = "Capybara: A computational tool to measure cell identity and fate transitions",
abstract = "Measuring cell identity in development, disease, and reprogramming is challenging as cell types and states are in continual transition. Here, we present Capybara, a computational tool to classify discrete cell identity and intermediate “hybrid” cell states, supporting a metric to quantify cell fate transition dynamics. We validate hybrid cells using experimental lineage tracing data to demonstrate the multi-lineage potential of these intermediate cell states. We apply Capybara to diagnose shortcomings in several cell engineering protocols, identifying hybrid states in cardiac reprogramming and off-target identities in motor neuron programming, which we alleviate by adding exogenous signaling factors. Further, we establish a putative in vivo correlate for induced endoderm progenitors. Together, these results showcase the utility of Capybara to dissect cell identity and fate transitions, prioritizing interventions to enhance the efficiency and fidelity of stem cell engineering.",
keywords = "cell differentiation, cell reprogramming, cell-type classification, hybrid cells, single-cell analysis",
author = "Wenjun Kong and Fu, {Yuheng C.} and Holloway, {Emily M.} and G{\"o}rkem Garipler and Xue Yang and Mazzoni, {Esteban O.} and Morris, {Samantha A.}",
note = "Funding Information: We thank members of the Morris laboratory for their helpful discussions; Barbara Treutlein for sharing the original QP code; Dennis Oakley of the Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children's Discovery Institute (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642); and Lee Grimes and Nathan Salomonis for helpful discussion on hybrid cell identity. Thank you also to Colin. This work was funded by National Institute of General Medical Sciences R01 GM126112 and Silicon Valley Community Foundation, Chan Zuckerberg Initiative Grant HCA2-A-1708-02799, both to S.A.M. and National Institute of General Medical Sciences R01 GM138876 to E.O.M.; S.A.M. is supported by an Allen Distinguished Investigator Award (through the Paul G. Allen Frontiers Group), a Vallee Scholar Award, a Sloan Research Fellowship, and a New York Stem Cell Foundation Robertson Investigator Award; W.K. is supported by a Douglas Covey Fellowship; and E.M.H. is supported by NIH/NHLBI T32 HL007317-44. Conceptualization, methodology, W.K. S.A.M.; Software, W.K.; Formal analysis, W.K. Y.C.F. X.Y.; Investigation, W.K. E.M.H. X.Y. G.G. E.O.M. S.A.M.; Data curation, W.K. Y.C.F.; Writing – original draft, W.K. S.A.M.; Writing – review & editing, W.K. E.M.H. X.Y. E.O.M. S.A.M.; Visualization, W.K. S.A.M.; Funding acquisition, resources, supervision, E.O.M. S.A.M. S.A.M. is on the advisory board of Cell Stem Cell. Funding Information: We thank members of the Morris laboratory for their helpful discussions; Barbara Treutlein for sharing the original QP code; Dennis Oakley of the Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642); and Lee Grimes and Nathan Salomonis for helpful discussion on hybrid cell identity. Thank you also to Colin. This work was funded by National Institute of General Medical Sciences R01 GM126112 and Silicon Valley Community Foundation, Chan Zuckerberg Initiative Grant HCA2-A-1708-02799 , both to S.A.M. and National Institute of General Medical Sciences R01 GM138876 to E.O.M.; S.A.M. is supported by an Allen Distinguished Investigator Award (through the Paul G. Allen Frontiers Group ), a Vallee Scholar Award , a Sloan Research Fellowship , and a New York Stem Cell Foundation Robertson Investigator Award; W.K. is supported by a Douglas Covey Fellowship ; and E.M.H. is supported by NIH/NHLBI T32 HL007317-44 . Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = apr,
day = "7",
doi = "10.1016/j.stem.2022.03.001",
language = "English (US)",
volume = "29",
pages = "635--649.e11",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}