Resolving Fates and Single-Cell Transcriptomes of Hematopoietic Stem Cell Clones by PolyloxExpress Barcoding

被引：107

作者：

Pei, Weike ^{[1
]}

Shang, Fuwei ^{[1
,2
]}

Wang, Xi ^{[1
,3
]}

Fanti, Ann-Kathrin ^{[1
]}

Greco, Alessandro ^{[3
,4
]}

Busch, Katrin ^{[1
]}

Klapproth, Kay ^{[1
]}

Zhang, Qin ^{[3
]}

Quedenau, Claudia ^{[5
]}

Sauer, Sascha ^{[5
]}

Feyerabend, Thorsten B. ^{[1
]}

Hoefer, Thomas ^{[3
]}

Rodewald, Hans-Reimer ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Cellular Immunol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, Fac Med, Neuenheimer Feld 672, D-69120 Heidelberg, Germany

[3] German Canc Res Ctr, Div Theoret Syst Biol, Neuenheimer Feld 580, D-69120 Heidelberg, Germany

[4] Heidelberg Univ, Fac Biosci, Neuenheimer Feld 234, D-69120 Heidelberg, Germany

[5] Max Delbruck Ctr, Sci Genom Platforms BIMSB BIH, Hannoversche Str 28, D-10115 Berlin, Germany

来源：

CELL STEM CELL | 2020年 / 27卷 / 03期

基金：

欧洲研究理事会;

关键词：

DIFFERENTIATION PROGRAMS; PROGENITOR CELLS; SELF-RENEWAL; EXPRESSION; DISTINCT; CRE; IDENTIFICATION; CYCLE;

D O I：

10.1016/j.stem.2020.07.018

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：383 / +

页数：21

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