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A proteomic roadmap of ribosome heterogeneity during human embryonic stem cell differentiation

ABSTRACT: Recent findings suggest that the ribosome itself modulates gene expression. However, whether ribosomes change composition across cell types to control cell fate remains unknown. To determine the magnitude of ribosome heterogeneity and its functional contribution to cell fate specification, we measured ribosomal protein abundance in actively translating ribosomes by quantitative mass spectrometry on a day-by-day basis as human embryonic stem cells differentiate in a step-wise fashion down endoderm and mesoderm lineages. We identified numerous core ribosomal proteins (RPs) as changing significantly in abundance in actively translating ribosomes during cell fate specification, including progressive decreases in ribosome incorporation for several ribosomal proteins during mesoderm differentiation. We further traced ribosome composition changes at the cytoplasmic, whole-cell, and mRNA transcript levels and identified multiple mechanisms regulating actively translating ribosome composition. These findings reveal extensive ribosomal remodeling during differentiation, suggesting that individual ribosomal components may have cell type-specific specialized translation functions.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Naomi Genuth

LAB HEAD: Maria Barna

PROVIDER: PXD032904 | Pride | 2022-09-19

REPOSITORIES: Pride

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