Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-aortic Cluster Architecture

Antoniana Batsivari, Stanislav Rybtsov, Celine Souilhol, Anahi Binagui-Casas, David Hills, Suling Zhao, Paul Travers, Alexander Medvinsky

Research output: Contribution to journalArticlepeer-review

Abstract

During development, hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region through a process of multi-step maturation and expansion. While proliferation of adult HSCs is implicated in the balance between self-renewal and differentiation, very little is known about the proliferation status of nascent HSCs in the AGM region. Using Fucci reporter mice that enable in vivo visualization of cell-cycle status, we detect increased proliferation during pre-HSC expansion followed by a slowing down of cycling once cells start to acquire a definitive HSC state, similar to fetal liver HSCs. We observe time-specific changes in intra-aortic hematopoietic clusters corresponding to HSC maturation stages. The proliferative architecture of the clusters is maintained in an orderly anatomical manner with slowly cycling cells at the base and more actively proliferating cells at the more apical part of the cluster, which correlates with c-KIT expression levels, thus providing an anatomical basis for the role of SCF in HSC maturation.

Original languageEnglish
Pages (from-to)1549-1562
JournalStem Cell Reports
Volume8
Issue number6
Early online date4 May 2017
DOIs
Publication statusPublished - 6 Jun 2017

Keywords

  • Haematopoietic stem cells
  • Fucci
  • proliferation

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