Developmental cues license megakaryocyte priming in murine hematopoietic stem cells

Trine Ahn Kristiansen, Qinyu Zhang, Stefano Vergani, Elena Boldrin, Niklas Krausse, Oscar André, Pontus Nordenfelt, Mikael Sigvardsson, David Bryder, Jonas Ungerbäck, Joan Yuan

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)6228-6241
Antal sidor27
TidskriftBlood Advances
Volym6
Nummer24
Tidigt onlinedatum2022 maj 18
DOI
StatusPublished - 2022

Bibliografisk information

Copyright © 2022 American Society of Hematology.

Ämnesklassifikation (UKÄ)

  • Hematologi

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