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Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age

Konturek-Ciesla, Anna LU ; Dhapola, Parashar LU ; Zhang, Qinyu LU ; Säwén, Petter LU ; Wan, Haixia LU ; Karlsson, Göran LU and Bryder, David LU (2023) In Cell Reports 42(4).
Abstract

Aging negatively affects hematopoiesis, with consequences for immunity and acquired blood cell disorders. Although impairments in hematopoietic stem cell (HSC) function contribute to this, the in vivo dynamics of such changes remain obscure. Here, we integrate extensive longitudinal functional assessments of HSC-specific lineage tracing with single-cell transcriptome and epitope profiling. In contrast to recent suggestions from single-cell RNA sequencing alone, our data favor a defined structure of HSC/progenitor differentiation that deviates substantially from HSC-derived hematopoiesis following transplantation. Native age-dependent attrition in HSC differentiation manifests as drastically reduced lymphoid output through an early... (More)

Aging negatively affects hematopoiesis, with consequences for immunity and acquired blood cell disorders. Although impairments in hematopoietic stem cell (HSC) function contribute to this, the in vivo dynamics of such changes remain obscure. Here, we integrate extensive longitudinal functional assessments of HSC-specific lineage tracing with single-cell transcriptome and epitope profiling. In contrast to recent suggestions from single-cell RNA sequencing alone, our data favor a defined structure of HSC/progenitor differentiation that deviates substantially from HSC-derived hematopoiesis following transplantation. Native age-dependent attrition in HSC differentiation manifests as drastically reduced lymphoid output through an early lymphoid-primed progenitor (MPP Ly-I). While in vitro activation fails to rescue lymphoid differentiation from most aged HSCs, robust lymphopoiesis can be achieved by culturing elevated numbers of candidate HSCs. Therefore, our data position rare chronologically aged HSC clones, fully competent at producing lymphoid offspring, as a prime target for approaches aimed to improve lymphopoiesis in the elderly.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aging, CITE-seq, CP: Cell biology, hematopoietic progenitors, hematopoietic stem cells, in vitro culture, lineage tracing, scRNA-seq
in
Cell Reports
volume
42
issue
4
article number
112304
publisher
Cell Press
external identifiers
  • pmid:36961818
  • scopus:85150832848
ISSN
2211-1247
DOI
10.1016/j.celrep.2023.112304
language
English
LU publication?
yes
id
42b02449-8c79-4a5a-9ba1-3b30cf3059b8
date added to LUP
2023-05-22 11:46:18
date last changed
2024-11-16 19:59:49
@article{42b02449-8c79-4a5a-9ba1-3b30cf3059b8,
  abstract     = {{<p>Aging negatively affects hematopoiesis, with consequences for immunity and acquired blood cell disorders. Although impairments in hematopoietic stem cell (HSC) function contribute to this, the in vivo dynamics of such changes remain obscure. Here, we integrate extensive longitudinal functional assessments of HSC-specific lineage tracing with single-cell transcriptome and epitope profiling. In contrast to recent suggestions from single-cell RNA sequencing alone, our data favor a defined structure of HSC/progenitor differentiation that deviates substantially from HSC-derived hematopoiesis following transplantation. Native age-dependent attrition in HSC differentiation manifests as drastically reduced lymphoid output through an early lymphoid-primed progenitor (MPP Ly-I). While in vitro activation fails to rescue lymphoid differentiation from most aged HSCs, robust lymphopoiesis can be achieved by culturing elevated numbers of candidate HSCs. Therefore, our data position rare chronologically aged HSC clones, fully competent at producing lymphoid offspring, as a prime target for approaches aimed to improve lymphopoiesis in the elderly.</p>}},
  author       = {{Konturek-Ciesla, Anna and Dhapola, Parashar and Zhang, Qinyu and Säwén, Petter and Wan, Haixia and Karlsson, Göran and Bryder, David}},
  issn         = {{2211-1247}},
  keywords     = {{aging; CITE-seq; CP: Cell biology; hematopoietic progenitors; hematopoietic stem cells; in vitro culture; lineage tracing; scRNA-seq}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2023.112304}},
  doi          = {{10.1016/j.celrep.2023.112304}},
  volume       = {{42}},
  year         = {{2023}},
}