Resolving Fates and Single-Cell Transcriptomes of Hematopoietic Stem Cell Clones by PolyloxExpress Barcoding.
Cell Stem Cell
; 27(3): 383-395.e8, 2020 09 03.
Article
in En
| MEDLINE
| ID: mdl-32783885
ABSTRACT
Lineage tracing reveals hematopoietic stem cell (HSC) fates, while single-cell RNA sequencing identifies snapshots of HSC transcriptomes. To obtain information on fate plus transcriptome in the same cell, we developed the PolyloxExpress allele, enabling Cre-recombinase-dependent RNA barcoding in situ. Linking fates to single HSC transcriptomes provided the information required to identify transcriptional signatures of HSC fates, which were not apparent in single-HSC transcriptomes alone. We find that differentiation-inactive, multilineage, and lineage-restricted HSC clones reside in distinct regions of the transcriptional landscape of hematopoiesis. Differentiation-inactive HSC clones are closer to the origin of the transcriptional trajectory, yet they are not characterized by a quiescent gene signature. Fate-specific gene signatures imply coherence of clonal HSC fates, and HSC output toward short-lived lineage progenitors indicates stability of HSC fates over time. These combined analyses of fate and transcriptome under physiological conditions may pave the way toward identifying molecular determinants of HSC fates.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematopoietic Stem Cells
/
Transcriptome
Language:
En
Journal:
Cell Stem Cell
Year:
2020
Document type:
Article
Affiliation country:
Alemania