Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction

Safi, Fatemeh LU ; Dhapola, Parashar LU ; Warsi, Sarah LU ; Sommarin, Mikael LU ; Erlandsson, Eva LU ; Ungerbäck, Jonas LU ; Warfvinge, Rebecca LU ; Sitnicka, Ewa LU ; Bryder, David LU and Böiers, Charlotta LU , et al. (2022) In Cell Reports 39(6).
Abstract

The emerging notion of hematopoietic stem and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular-fate options emerge and at which stem-like stage lineage priming is initiated. Here, we investigate single-cell chromatin accessibility of Lineage-, cKit+, and Sca1+ (LSK) HSPCs spanning the early differentiation landscape. Application of a signal-processing algorithm to detect transition points corresponding to massive alterations in accessibility of 571 transcription factor motifs reveals a population of LSK FMS-like tyrosine kinase 3 (Flt3)intCD9high cells that concurrently display stem-like and lineage-affiliated chromatin signatures, pointing to a... (More)

The emerging notion of hematopoietic stem and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular-fate options emerge and at which stem-like stage lineage priming is initiated. Here, we investigate single-cell chromatin accessibility of Lineage-, cKit+, and Sca1+ (LSK) HSPCs spanning the early differentiation landscape. Application of a signal-processing algorithm to detect transition points corresponding to massive alterations in accessibility of 571 transcription factor motifs reveals a population of LSK FMS-like tyrosine kinase 3 (Flt3)intCD9high cells that concurrently display stem-like and lineage-affiliated chromatin signatures, pointing to a simultaneous gain of both lympho-myeloid and megakaryocyte-erythroid programs. Molecularly and functionally, these cells position between stem cells and committed progenitors and display multi-lineage capacity in vitro and in vivo but lack self-renewal activity. This integrative molecular analysis resolves the heterogeneity of cells along hematopoietic differentiation and permits investigation of chromatin-mediated transition between multipotency and lineage restriction.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
39
issue
6
article number
110798
publisher
Cell Press
external identifiers
  • scopus:85129924068
  • pmid:35545037
ISSN
2211-1247
DOI
10.1016/j.celrep.2022.110798
language
English
LU publication?
yes
additional info
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
id
b44c023b-695f-4c55-8c83-b747fa1f3b6e
date added to LUP
2022-05-12 13:23:56
date last changed
2025-03-07 14:55:29
@article{b44c023b-695f-4c55-8c83-b747fa1f3b6e,
  abstract     = {{<p>The emerging notion of hematopoietic stem and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular-fate options emerge and at which stem-like stage lineage priming is initiated. Here, we investigate single-cell chromatin accessibility of Lineage-, cKit+, and Sca1+ (LSK) HSPCs spanning the early differentiation landscape. Application of a signal-processing algorithm to detect transition points corresponding to massive alterations in accessibility of 571 transcription factor motifs reveals a population of LSK FMS-like tyrosine kinase 3 (Flt3)intCD9high cells that concurrently display stem-like and lineage-affiliated chromatin signatures, pointing to a simultaneous gain of both lympho-myeloid and megakaryocyte-erythroid programs. Molecularly and functionally, these cells position between stem cells and committed progenitors and display multi-lineage capacity in vitro and in vivo but lack self-renewal activity. This integrative molecular analysis resolves the heterogeneity of cells along hematopoietic differentiation and permits investigation of chromatin-mediated transition between multipotency and lineage restriction.</p>}},
  author       = {{Safi, Fatemeh and Dhapola, Parashar and Warsi, Sarah and Sommarin, Mikael and Erlandsson, Eva and Ungerbäck, Jonas and Warfvinge, Rebecca and Sitnicka, Ewa and Bryder, David and Böiers, Charlotta and Thakur, Ram Krishna and Karlsson, Göran}},
  issn         = {{2211-1247}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{6}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2022.110798}},
  doi          = {{10.1016/j.celrep.2022.110798}},
  volume       = {{39}},
  year         = {{2022}},
}