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Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level

Kristiansen, Trine A. LU ; Jaensson Gyllenbäck, Elin LU ; Zriwil, Alya LU ; Björklund, Tomas LU ; Daniel, Jeremy A.; Sitnicka, Ewa LU ; Soneji, Shamit LU ; Bryder, David LU and Yuan, Joan LU (2016) In Immunity 45(2). p.346-357
Abstract

Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to... (More)

Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to fetal-like elevated self-renewal and repopulation potential. These results anchor the attenuation of B-1a cell output to fetal HSC behavior and demonstrate that the developmental decline in regenerative potential represents a reversible HSC state.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Immunity
volume
45
issue
2
pages
12 pages
publisher
Cell Press
external identifiers
  • scopus:85002548279
  • wos:000382267300016
ISSN
1074-7613
DOI
10.1016/j.immuni.2016.07.014
language
English
LU publication?
yes
id
a12a38e8-c299-4a98-8150-c3a94fac36e5
date added to LUP
2016-12-30 13:53:48
date last changed
2017-10-22 05:24:34
@article{a12a38e8-c299-4a98-8150-c3a94fac36e5,
  abstract     = {<p>Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to fetal-like elevated self-renewal and repopulation potential. These results anchor the attenuation of B-1a cell output to fetal HSC behavior and demonstrate that the developmental decline in regenerative potential represents a reversible HSC state.</p>},
  author       = {Kristiansen, Trine A. and Jaensson Gyllenbäck, Elin and Zriwil, Alya and Björklund, Tomas and Daniel, Jeremy A. and Sitnicka, Ewa and Soneji, Shamit and Bryder, David and Yuan, Joan},
  issn         = {1074-7613},
  language     = {eng},
  number       = {2},
  pages        = {346--357},
  publisher    = {Cell Press},
  series       = {Immunity},
  title        = {Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level},
  url          = {http://dx.doi.org/10.1016/j.immuni.2016.07.014},
  volume       = {45},
  year         = {2016},
}