On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI)...On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.展开更多
Now increasing chemical modifications are discovered on genomic DNA and RNA. Up to date, more than150 chemical modifications are identified in nucleic acids. These chemical modifications do not change the sequence of ...Now increasing chemical modifications are discovered on genomic DNA and RNA. Up to date, more than150 chemical modifications are identified in nucleic acids. These chemical modifications do not change the sequence of DNA and RNA, but alter their structures and biochemical properties, and eventually control or regulate the spatial and temporal expression of genes. Elucidation of the functional roles of these modifications is vital to our understanding of living organisms. However, the modifications in DNA and RNA generally have extremely low abundance in vivo. Therefore, sensitive and specific detection methods are essential to decipher the functional roles of these modifications. Chemical derivatization in combination with mass spectrometry(MS) analysis has been proved to be a promising strategy to efficiently analyze these modifications in DNA and RNA. In the last several years, many chemical derivatization-MS-based analytical methods were established for the sensitive and effective analysis of nucleic acid modifications. In this review, we summarize the recent advances for deciphering modifications in DNA and RNA by chemical derivatization-MS analysis. We hope this review can stimulate the future studies of DNA and RNA modifications.展开更多
基金supported by the National Natural Science Foundation of China(No.21927808)the Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(CIFMS,Nos.2022-I2M-2-002 and 2021-1-I2M-028).
文摘On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.
基金supported by the National Key R&D Program of China (No. 2017YFC0906800)the National Natural Science Foundation of China (Nos. 21522507, 21672166, 21635006 and 21721005)
文摘Now increasing chemical modifications are discovered on genomic DNA and RNA. Up to date, more than150 chemical modifications are identified in nucleic acids. These chemical modifications do not change the sequence of DNA and RNA, but alter their structures and biochemical properties, and eventually control or regulate the spatial and temporal expression of genes. Elucidation of the functional roles of these modifications is vital to our understanding of living organisms. However, the modifications in DNA and RNA generally have extremely low abundance in vivo. Therefore, sensitive and specific detection methods are essential to decipher the functional roles of these modifications. Chemical derivatization in combination with mass spectrometry(MS) analysis has been proved to be a promising strategy to efficiently analyze these modifications in DNA and RNA. In the last several years, many chemical derivatization-MS-based analytical methods were established for the sensitive and effective analysis of nucleic acid modifications. In this review, we summarize the recent advances for deciphering modifications in DNA and RNA by chemical derivatization-MS analysis. We hope this review can stimulate the future studies of DNA and RNA modifications.
