A single-cell Raman-based platform to identify developmental stages of human pluripotent stem cell-derived neurons

Proceedings of the National Academy of Sciences of the United States of America
Chia-Chen HsuHua Ye

Abstract

Stem cells with the capability to self-renew and differentiate into multiple cell derivatives provide platforms for drug screening and promising treatment options for a wide variety of neural diseases. Nevertheless, clinical applications of stem cells have been hindered partly owing to a lack of standardized techniques to characterize cell molecular profiles noninvasively and comprehensively. Here, we demonstrate that a label-free and noninvasive single-cell Raman microspectroscopy (SCRM) platform was able to identify neural cell lineages derived from clinically relevant human induced pluripotent stem cells (hiPSCs). By analyzing the intrinsic biochemical profiles of single cells at a large scale (8,774 Raman spectra in total), iPSCs and iPSC-derived neural cells can be distinguished by their intrinsic phenotypic Raman spectra. We identified a Raman biomarker from glycogen to distinguish iPSCs from their neural derivatives, and the result was verified by the conventional glycogen detection assays. Further analysis with a machine learning classification model, utilizing t-distributed stochastic neighbor embedding (t-SNE)-enhanced ensemble stacking, clearly categorized hiPSCs in different developmental stages with 97.5% accuracy....Continue Reading

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Citations

Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesca RaveraHugh J Byrne
Nov 10, 2020·Computational and Structural Biotechnology Journal·Ya-Juan LiuXi-Yong Yu
Jun 8, 2021·Cell Reports Medicine·John DePaolo, Scott M Damrauer
Jun 17, 2021·Stem Cell Reviews and Reports·Daniela S C BispoAna M Gil

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Methods Mentioned

BETA
PCA
feature extraction
electron microscopy
PCR
Fluorescence Microscopy
Assay

Software Mentioned

R
house
SNE
qBase Plus
geNorm
SCRS
Rt
LinRegPCR

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