Developmental cues license megakaryocyte priming in murine hematopoietic stem cells
(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.
(Less)
- author
- organization
-
- Developmental Immunology (research group)
- Division of Molecular Hematology (DMH)
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Developmental Hematopoiesis (research group)
- Infection Medicine (BMC)
- Department of Clinical Sciences, Lund
- Molecular Lymphopoiesis (research group)
- publishing date
- 2022-05-18
- 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
-
- scopus:85140399432
- pmid:35584393
- 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
- 2024-09-07 09:12:25
@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}}, }