Single-Cell Proteo-Transcriptomic Profiling Uncovers Post-Translational Regulatory Layers in Human Hematopoiesis
- 1University of Cambridge
Abstract
Background: Hematopoietic stem cells (HSCs) have the unique ability to produce all mature cell types in the blood and understanding the mechanisms governing their differentiation and renewal is a driving question in stem cell biology. While single-cell RNA sequencing has transformed our view of human hematopoiesis, mRNA abundance represents an incomplete proxy for functional cell states. Here, we apply single-cell multimodal profiling to simultaneously measure 280 surface and intracellular protein targets alongside whole transcriptomes within individual adult human hematopoietic stem and progenitor cells. Results: By directly coupling modalities within single cells, we show that protein-RNA correlations peak dynamically in transitioning intermediate progenitors across lineages, consistent with pervasive post-transcriptional mechanics underlying lineage choice. Furthermore, key transcription factor proteins maintain multilineage co-expression longer into commitment than their transcripts, demarcating a possible window of fate decision reversibility. Moreover, low and flat CTNNB1 mRNA levels mask late-erythroid {beta}-catenin protein enrichment, apparently pairing with E-cadherin expression and suggesting post-translational stabilization at the cell membrane. Conclusions: This dataset enables the observation of translational dynamics and RNA-protein relationships throughout the differentiation landscape at an unprecedented level of granularity. Together, our findings demonstrate that transcriptomics alone misses fundamental regulatory programs, establishing single-cell proteo-transcriptomics as a powerful tool for decoding human stem cell fate.
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BibTeX
@misc{gollin2026singlecell,
title = {{Single-Cell Proteo-Transcriptomic Profiling Uncovers Post-Translational Regulatory Layers in Human Hematopoiesis}},
author = {J. Gollin and N. Garcia-Gisbert and T. Isobe and E. Laurenti and B. Gottgens and A. Yang and N. K. Wilson},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757909},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757909v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Single-Cell Proteo-Transcriptomic Profiling Uncovers Post-Translational Regulatory Layers in Human Hematopoiesis
AU - J. Gollin
AU - N. Garcia-Gisbert
AU - T. Isobe
AU - E. Laurenti
AU - B. Gottgens
AU - A. Yang
AU - N. K. Wilson
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757909
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757909v1
AB - Background: Hematopoietic stem cells (HSCs) have the unique ability to produce all mature cell types in the blood and understanding the mechanisms governing their differentiation and renewal is a driving question in stem cell biology. While single-cell RNA sequencing has transformed our view of human hematopoiesis, mRNA abundance represents an incomplete proxy for functional cell states. Here, we apply single-cell multimodal profiling to simultaneously measure 280 surface and intracellular protein targets alongside whole transcriptomes within individual adult human hematopoietic stem and progenitor cells. Results: By directly coupling modalities within single cells, we show that protein-RNA correlations peak dynamically in transitioning intermediate progenitors across lineages, consistent with pervasive post-transcriptional mechanics underlying lineage choice. Furthermore, key transcription factor proteins maintain multilineage co-expression longer into commitment than their transcripts, demarcating a possible window of fate decision reversibility. Moreover, low and flat CTNNB1 mRNA levels mask late-erythroid {beta}-catenin protein enrichment, apparently pairing with E-cadherin expression and suggesting post-translational stabilization at the cell membrane. Conclusions: This dataset enables the observation of translational dynamics and RNA-protein relationships throughout the differentiation landscape at an unprecedented level of granularity. Together, our findings demonstrate that transcriptomics alone misses fundamental regulatory programs, establishing single-cell proteo-transcriptomics as a powerful tool for decoding human stem cell fate.
ER -