@article{fc2f8b6571e24642bcedb61f023866e8,
title = "Multi-Omic Analyses of Growth Cones at Different Developmental Stages Provides Insight into Pathways in Adult Neuroregeneration",
abstract = "Growth cones (GCs) are structures associated with growing neurons. GC membrane expansion, which necessitates protein-lipid interactions, is critical to axonal elongation in development and in adult neuritogenesis. We present a multi-omic analysis that integrates proteomics and lipidomics data for the identification of GC pathways, cell phenotypes, and lipid-protein interactions, with an analytic platform to facilitate the visualization of these data. We combine lipidomic data from GC and adult axonal regeneration following optic nerve crush. Our results reveal significant molecular variability in GCs across developmental ages that aligns with the upregulation and downregulation of lipid metabolic processes and correlates with distinct changes in the lipid composition of GC plasmalemma. We find that these processes also define the transition into a growth-permissive state in the adult central nervous system. The insight derived from these analyses will aid in promoting adult regeneration and functional innervation in devastating neurodegenerative diseases.",
keywords = "Biological Sciences, Lipidomics, Omics, Proteomics, Systems Biology",
author = "Chauhan, {Muhammad Zain} and Jennifer Arcuri and Park, {Kevin K.} and Zafar, {Maroof Khan} and Rabeet Fatmi and Hackam, {Abigail S.} and Yuqin Yin and Larry Benowitz and Goldberg, {Jeffrey L.} and Mohammad Samarah and Bhattacharya, {Sanjoy K.}",
note = "Funding Information: We thank Ciara Myer and Bryan Alfonso for assistance with mass spectrometry and Dr. Anna Trzeciecka for GCM proteomics data. We thank Drs. Hiroyuki Kamiguchi (RIKEN), Alicia K. Byrd (University of Arkansas for Medical Sciences), and Vance Lemmon (University of Miami) for their critical comments on the manuscript. This work was supported by an unrestricted grant from Research to Prevent Blindness; United States Department of Defense grants W81XWH-15-1-0079 and W81XWH-16-1-0715 , and NIH , United States Grants EY14801 , EY026546 , U01EY027257 , and U01EY027261 . Metabolomics workbench is an effort of NIH Common Fund's Metabolomics Data Repository and Coordinating Center supported by U2C DK119886 . Funding Information: We thank Ciara Myer and Bryan Alfonso for assistance with mass spectrometry and Dr. Anna Trzeciecka for GCM proteomics data. We thank Drs. Hiroyuki Kamiguchi (RIKEN), Alicia K. Byrd (University of Arkansas for Medical Sciences), and Vance Lemmon (University of Miami) for their critical comments on the manuscript. This work was supported by an unrestricted grant from Research to Prevent Blindness; United States Department of Defense grants W81XWH-15-1-0079 and W81XWH-16-1-0715, and NIH, United States Grants EY14801, EY026546, U01EY027257, and U01EY027261. Metabolomics workbench is an effort of NIH Common Fund's Metabolomics Data Repository and Coordinating Center supported by U2C DK119886. S.K.B. conceived the study. M.Z.C. and J.A. carried out the proteomics and lipidomics analysis. K.K.P. and A.S.H. performed optic nerve regeneration experiments utilizing PtenKO, Socs KO, and Wnt3a-mediated regeneration data, Y.Y. L.B. and J.L.G provided optic nerve crush versus regeneration data. M.K.Z. assisted in protein-lipid interaction data analysis. R.F. and M.S. developed computational tools with assistance from M.Z.C. and S.K.B. M.Z.C. and S.K.B. co-wrote the manuscript. M.Z.C. M.K.Z. M.S. A.S.H. and S.K.B. wrote the Transparent Methods (see Supplemental Information) and the legends of the figures. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = feb,
day = "21",
doi = "10.1016/j.isci.2020.100836",
language = "English",
volume = "23",
journal = "iScience",
issn = "2589-0042",
number = "2",
}