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Developmental cues license megakaryocyte priming in murine hematopoietic stem cells

Kristiansen, Trine Ahn LU ; Zhang, Qinyu LU ; Vergani, Stefano LU ; Boldrin, Elena LU ; Krausse, Niklas LU ; André, Oscar LU ; Nordenfelt, Pontus LU orcid ; Sigvardsson, Mikael LU ; Bryder, David LU and Ungerbäck, Jonas LU , et al. (2022) In Blood Advances 6(24). p.6228-6241
Abstract

The fetal to adult switch in hematopoietic stem cell (HSC) behavior is characterized by alterations in lineage output and entry into deep quiescence. Here we identify the emergence of megakaryocyte (Mk) biased HSCs as an event coinciding with this developmental switch. Single-cell chromatin accessibility analysis reveals a ubiquitous acquisition of Mk lineage priming signatures in HSCs during the fetal to adult transition. These molecular changes functionally coincide with an increased amplitude of early Mk differentiation events following acute inflammatory insult. Importantly, we identify LIN28B - known for its role in promoting fetal-like self-renewal, as an insulator against the establishment of a Mk biased HSC pool. LIN28B protein... (More)

The fetal to adult switch in hematopoietic stem cell (HSC) behavior is characterized by alterations in lineage output and entry into deep quiescence. Here we identify the emergence of megakaryocyte (Mk) biased HSCs as an event coinciding with this developmental switch. Single-cell chromatin accessibility analysis reveals a ubiquitous acquisition of Mk lineage priming signatures in HSCs during the fetal to adult transition. These molecular changes functionally coincide with an increased amplitude of early Mk differentiation events following acute inflammatory insult. Importantly, we identify LIN28B - known for its role in promoting fetal-like self-renewal, as an insulator against the establishment of a Mk biased HSC pool. LIN28B protein is developmentally silenced in the third week of life and its prolonged expression delays emergency platelet output in young adult mice. We propose that developmental regulation of Mk priming may represent a switch for HSCs to toggle between prioritizing self-renewal in the fetus and increased host protection in postnatal life.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Advances
volume
6
issue
24
pages
27 pages
publisher
American Society of Hematology
external identifiers
  • pmid:35584393
  • scopus:85140399432
ISSN
2473-9529
DOI
10.1182/bloodadvances.2021006861
language
English
LU publication?
yes
additional info
Copyright © 2022 American Society of Hematology.
id
ccf5ce3a-00b9-4b2b-9762-e12c36450b0a
date added to LUP
2022-11-08 07:51:58
date last changed
2024-06-15 01:06:46
@article{ccf5ce3a-00b9-4b2b-9762-e12c36450b0a,
  abstract     = {{<p>The fetal to adult switch in hematopoietic stem cell (HSC) behavior is characterized by alterations in lineage output and entry into deep quiescence. Here we identify the emergence of megakaryocyte (Mk) biased HSCs as an event coinciding with this developmental switch. Single-cell chromatin accessibility analysis reveals a ubiquitous acquisition of Mk lineage priming signatures in HSCs during the fetal to adult transition. These molecular changes functionally coincide with an increased amplitude of early Mk differentiation events following acute inflammatory insult. Importantly, we identify LIN28B - known for its role in promoting fetal-like self-renewal, as an insulator against the establishment of a Mk biased HSC pool. LIN28B protein is developmentally silenced in the third week of life and its prolonged expression delays emergency platelet output in young adult mice. We propose that developmental regulation of Mk priming may represent a switch for HSCs to toggle between prioritizing self-renewal in the fetus and increased host protection in postnatal life.</p>}},
  author       = {{Kristiansen, Trine Ahn and Zhang, Qinyu and Vergani, Stefano and Boldrin, Elena and Krausse, Niklas and André, Oscar and Nordenfelt, Pontus and Sigvardsson, Mikael and Bryder, David and Ungerbäck, Jonas and Yuan, Joan}},
  issn         = {{2473-9529}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{24}},
  pages        = {{6228--6241}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood Advances}},
  title        = {{Developmental cues license megakaryocyte priming in murine hematopoietic stem cells}},
  url          = {{http://dx.doi.org/10.1182/bloodadvances.2021006861}},
  doi          = {{10.1182/bloodadvances.2021006861}},
  volume       = {{6}},
  year         = {{2022}},
}