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Mitotic History Reveals Distinct Stem Cell Populations and Their Contributions to Hematopoiesis

Säwén, Petter LU ; Lang, Stefan LU ; Mandal, Pankaj; Rossi, Derrick J; Soneji, Shamit LU and Bryder, David LU (2016) In Cell Reports 14(12). p.2809-2818
Abstract

Homeostasis of short-lived blood cells is dependent on rapid proliferation of immature precursors. Using a conditional histone 2B-mCherry-labeling mouse model, we characterize hematopoietic stem cell (HSC) and progenitor proliferation dynamics in steady state and following several types of induced stress. HSC proliferation following HSC transplantation into lethally irradiated mice is fundamentally different not only from native hematopoiesis but also from other stress contexts. Whereas transplantation promoted sustained, long-term proliferation of HSCs, both cytokine-induced mobilization and acute depletion of selected blood cell lineages elicited very limited recruitment of HSCs to the proliferative pool. By coupling mCherry-based... (More)

Homeostasis of short-lived blood cells is dependent on rapid proliferation of immature precursors. Using a conditional histone 2B-mCherry-labeling mouse model, we characterize hematopoietic stem cell (HSC) and progenitor proliferation dynamics in steady state and following several types of induced stress. HSC proliferation following HSC transplantation into lethally irradiated mice is fundamentally different not only from native hematopoiesis but also from other stress contexts. Whereas transplantation promoted sustained, long-term proliferation of HSCs, both cytokine-induced mobilization and acute depletion of selected blood cell lineages elicited very limited recruitment of HSCs to the proliferative pool. By coupling mCherry-based analysis of proliferation history with multiplex gene expression analyses on single cells, we have found that HSCs can be stratified into four distinct subtypes. These subtypes have distinct molecular signatures and differ significantly in their reconstitution potentials, showcasing the power of tracking proliferation history when resolving functional heterogeneity of HSCs.

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organization
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Contribution to journal
publication status
published
subject
in
Cell Reports
volume
14
issue
12
pages
10 pages
publisher
Cell Press
external identifiers
  • Scopus:84961218486
  • WOS:000372869300005
ISSN
2211-1247
DOI
10.1016/j.celrep.2016.02.073
language
English
LU publication?
yes
id
cefb35a0-f55a-4677-a75c-9728d84cd37e
date added to LUP
2016-04-13 15:02:12
date last changed
2017-01-22 04:29:14
@article{cefb35a0-f55a-4677-a75c-9728d84cd37e,
  abstract     = {<p>Homeostasis of short-lived blood cells is dependent on rapid proliferation of immature precursors. Using a conditional histone 2B-mCherry-labeling mouse model, we characterize hematopoietic stem cell (HSC) and progenitor proliferation dynamics in steady state and following several types of induced stress. HSC proliferation following HSC transplantation into lethally irradiated mice is fundamentally different not only from native hematopoiesis but also from other stress contexts. Whereas transplantation promoted sustained, long-term proliferation of HSCs, both cytokine-induced mobilization and acute depletion of selected blood cell lineages elicited very limited recruitment of HSCs to the proliferative pool. By coupling mCherry-based analysis of proliferation history with multiplex gene expression analyses on single cells, we have found that HSCs can be stratified into four distinct subtypes. These subtypes have distinct molecular signatures and differ significantly in their reconstitution potentials, showcasing the power of tracking proliferation history when resolving functional heterogeneity of HSCs.</p>},
  author       = {Säwén, Petter and Lang, Stefan and Mandal, Pankaj and Rossi, Derrick J and Soneji, Shamit and Bryder, David},
  issn         = {2211-1247},
  language     = {eng},
  number       = {12},
  pages        = {2809--2818},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Mitotic History Reveals Distinct Stem Cell Populations and Their Contributions to Hematopoiesis},
  url          = {http://dx.doi.org/10.1016/j.celrep.2016.02.073},
  volume       = {14},
  year         = {2016},
}