Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis.

Nature
Alejo E Rodriguez-FraticelliFernando D Camargo

Abstract

Bone marrow transplantation therapy relies on the life-long regenerative capacity of haematopoietic stem cells (HSCs)1,2. HSCs present a complex variety of regenerative behaviours at the clonal level, but the mechanisms underlying this diversity are still undetermined3-11. Recent advances in single-cell RNA sequencing have revealed transcriptional differences among HSCs, providing a possible explanation for their functional heterogeneity12-17. However, the destructive nature of sequencing assays prevents simultaneous observation of stem cell state and function. To solve this challenge, we implemented expressible lentiviral barcoding, which enabled simultaneous analysis of lineages and transcriptomes from single adult HSCs and their clonal trajectories during long-term bone marrow reconstitution. Analysis of differential gene expression between clones with distinct behaviour revealed an intrinsic molecular signature that characterizes functional long-term repopulating HSCs. Probing this signature through in vivo CRISPR screening, we found the transcription factor TCF15 to be required and sufficient to drive HSC quiescence and long-term self-renewal. In situ, Tcf15 expression labels the most primitive subset of true multipotent H...Continue Reading

References

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Jan 13, 2018·Nature·Alejo E Rodriguez-FraticelliFernando D Camargo
Jan 25, 2018·Nature·Elisa Laurenti, Berthold Göttgens

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Citations

Oct 18, 2020·International Journal of Molecular Sciences·Emma C JosefssonChloe James
Nov 10, 2020·Blood Advances·Vinothini GovindarajahDamien Reynaud
Dec 3, 2020·Current Opinion in Hematology·Alejo E Rodriguez-Fraticelli, Fernando Camargo
Feb 11, 2021·Immunological Reviews·Nicoletta CaronniRenato Ostuni
Mar 19, 2021·Disease Models & Mechanisms·Paulina M Strzelecka, Frederik Damm
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Anna L HövingJohannes F W Greiner
Aug 18, 2020·Mechanisms of Ageing and Development·Hagai Yanai, Isabel Beerman
Apr 27, 2021·Current Opinion in Hematology·Jorge D Martin-Rufino, Vijay G Sankaran
Jun 5, 2021·Cell Stem Cell·Daniel Naveed TavakolGordana Vunjak-Novakovic
May 18, 2021·Current Opinion in Systems Biology·Lingfei WangLuca Pinello
Sep 13, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Byung-Chul LeeCynthia E Dunbar
Sep 9, 2021·The FEBS Journal·Izabella SkulimowskaKrzysztof Szade

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Methods Mentioned

BETA
inDrop
RNA-seq
scRNA-seq
PCR
in
inDrops
DNA-seq
FACS

Software Mentioned

tools
LARRY
Vectorbuilder
Addgene
inDrops
SPRING
MAGeCK
FlowJo
inDrop
Toppgene

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