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Ex vivo expansion potential of murine hematopoietic stem cells is a rare property only partially predicted by phenotype

Zhang, Qinyu LU orcid ; Olofzon, Rasmus LU orcid ; Konturek-Ciesla, Anna LU ; Yuan, Ouyang LU and Bryder, David LU (2024) In eLife 12.
Abstract

The scarcity of hematopoietic stem cells (HSCs) restricts their use in both clinical settings and experimental research. Here, we examined a recently developed method for expanding rigorously purified murine HSCs ex vivo. After 3 weeks of culture, only 0.1% of cells exhibited the input HSC phenotype, but these accounted for almost all functional long-term HSC activity. Input HSCs displayed varying potential for ex vivo self-renewal, with alternative outcomes revealed by single-cell multimodal RNA and ATAC sequencing profiling. While most HSC progeny offered only transient in vivo reconstitution, these cells efficiently rescued mice from lethal myeloablation. The amplification of functional HSC activity allowed for long-term multilineage... (More)

The scarcity of hematopoietic stem cells (HSCs) restricts their use in both clinical settings and experimental research. Here, we examined a recently developed method for expanding rigorously purified murine HSCs ex vivo. After 3 weeks of culture, only 0.1% of cells exhibited the input HSC phenotype, but these accounted for almost all functional long-term HSC activity. Input HSCs displayed varying potential for ex vivo self-renewal, with alternative outcomes revealed by single-cell multimodal RNA and ATAC sequencing profiling. While most HSC progeny offered only transient in vivo reconstitution, these cells efficiently rescued mice from lethal myeloablation. The amplification of functional HSC activity allowed for long-term multilineage engraftment in unconditioned hosts that associated with a return of HSCs to quiescence. Thereby, our findings identify several key considerations for ex vivo HSC expansion, with major implications also for assessment of normal HSC activity.

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; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ex vivo expansion, hematopoietic stem cell, mouse, regenerative medicine, stem cells, transplantation
in
eLife
volume
12
article number
RP91826
publisher
eLife Sciences Publications
external identifiers
  • pmid:38446538
  • scopus:85187199409
ISSN
2050-084X
DOI
10.7554/eLife.91826
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023, Zhang et al.
id
64377f95-5fcd-4cfb-8c4e-1490c3f19805
date added to LUP
2025-03-24 15:51:18
date last changed
2025-05-05 15:54:18
@article{64377f95-5fcd-4cfb-8c4e-1490c3f19805,
  abstract     = {{<p>The scarcity of hematopoietic stem cells (HSCs) restricts their use in both clinical settings and experimental research. Here, we examined a recently developed method for expanding rigorously purified murine HSCs ex vivo. After 3 weeks of culture, only 0.1% of cells exhibited the input HSC phenotype, but these accounted for almost all functional long-term HSC activity. Input HSCs displayed varying potential for ex vivo self-renewal, with alternative outcomes revealed by single-cell multimodal RNA and ATAC sequencing profiling. While most HSC progeny offered only transient in vivo reconstitution, these cells efficiently rescued mice from lethal myeloablation. The amplification of functional HSC activity allowed for long-term multilineage engraftment in unconditioned hosts that associated with a return of HSCs to quiescence. Thereby, our findings identify several key considerations for ex vivo HSC expansion, with major implications also for assessment of normal HSC activity.</p>}},
  author       = {{Zhang, Qinyu and Olofzon, Rasmus and Konturek-Ciesla, Anna and Yuan, Ouyang and Bryder, David}},
  issn         = {{2050-084X}},
  keywords     = {{ex vivo expansion; hematopoietic stem cell; mouse; regenerative medicine; stem cells; transplantation}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{eLife Sciences Publications}},
  series       = {{eLife}},
  title        = {{Ex vivo expansion potential of murine hematopoietic stem cells is a rare property only partially predicted by phenotype}},
  url          = {{http://dx.doi.org/10.7554/eLife.91826}},
  doi          = {{10.7554/eLife.91826}},
  volume       = {{12}},
  year         = {{2024}},
}