RT Journal Article
SR Electronic
T1 Ultrafast immunostaining of organ-scale tissues for scalable proteomic phenotyping
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 660373
DO 10.1101/660373
A1 Dae Hee Yun
A1 Young-Gyun Park
A1 Jae Hun Cho
A1 Lee Kamentsky
A1 Nicholas B. Evans
A1 Alex Albanese
A1 Katherine Xie
A1 Justin Swaney
A1 Chang Ho Sohn
A1 Yuxuan Tian
A1 Qiangge Zhang
A1 Gabi Drummond
A1 Webster Guan
A1 Nicholas DiNapoli
A1 Heejin Choi
A1 Hae-Yoon Jung
A1 Luzdary Ruelas
A1 Guoping Feng
A1 Kwanghun Chung
YR 2019
UL http://biorxiv.org/content/early/2019/06/05/660373.abstract
AB Studying the function and dysfunction of complex biological systems necessitates comprehensive understanding of individual cells. Advancements in three-dimensional (3D) tissue processing and imaging modalities have enabled rapid visualization and phenotyping of cells in their spatial context. However, system-wide interrogation of individual cells within large intact tissue remains challenging, low throughput, and error-prone owing to the lack of robust labeling technologies. Here we introduce a rapid, versatile, and scalable method, eFLASH, that enables complete and uniform labeling of organ-scale tissue within one day. eFLASH dynamically modulates chemical transport and reaction kinetics to establish system-wide uniform labeling conditions throughout the day-long labeling period. This unique approach enables the same protocol to be compatible with a wide range of tissue types and probes, enabling combinatorial molecular phenotyping across different organs and species. We applied eFLASH to generate quantitative maps of various cell types in mouse brains. We also demonstrated multidimensional cell profiling in a marmoset brain block. We envision that eFLASH will spur holistic phenotyping of emerging animal models and disease models to help assess their functions and dysfunctions.