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Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging

Säwen, Petter LU ; Eldeeb, Mohamed LU ; Erlandsson, Eva LU ; Kristiansen, Trine A. LU ; Laterza, Cecilia LU ; Kokaia, Zaal LU ; Karlsson, Göran LU ; Yuan, Joan LU ; Soneji, Shamit LU and Mandal, Pankaj K., et al. (2018) In eLife 7.
Abstract

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC... (More)

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.

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keywords
aging, hematopoiesis, lineage tracing, mouse, regenerative medicine, steady state, stem cells
in
eLife
volume
7
publisher
eLife Sciences Publications LTD.
external identifiers
  • scopus:85058736032
ISSN
2050-084X
DOI
10.7554/eLife.41258
language
English
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yes
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542886fe-51be-44ac-b211-ef410a010993
date added to LUP
2019-01-03 10:54:13
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2019-10-08 03:43:37
@article{542886fe-51be-44ac-b211-ef410a010993,
  abstract     = {<p>A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.</p>},
  articleno    = {e41258},
  author       = {Säwen, Petter and Eldeeb, Mohamed and Erlandsson, Eva and Kristiansen, Trine A. and Laterza, Cecilia and Kokaia, Zaal and Karlsson, Göran and Yuan, Joan and Soneji, Shamit and Mandal, Pankaj K. and Rossi, Derrick J. and Bryder, David},
  issn         = {2050-084X},
  keyword      = {aging,hematopoiesis,lineage tracing,mouse,regenerative medicine,steady state,stem cells},
  language     = {eng},
  month        = {12},
  publisher    = {eLife Sciences Publications LTD.},
  series       = {eLife},
  title        = {Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging},
  url          = {http://dx.doi.org/10.7554/eLife.41258},
  volume       = {7},
  year         = {2018},
}