Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade Journal Article

   


Authors: Khong, D. M.; Dudakov, J. A.; Hammett, M. V.; Jurblum, M. I.; Khong, S. M. L.; Goldberg, G. L.; Ueno, T.; Spyroglou, L.; Young, L. F.; van den Brink, M. R. M.; Boyd, R. L.; Chidgey, A. P.
Article Title: Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade
Abstract: Mechanisms underlying age-related defects within lymphoid-lineages remain poorly understood. We previously reported that sex steroid ablation (SSA) induced lymphoid rejuvenation and enhanced recovery from hematopoietic stem cell (HSC) transplantation (HSCT). We herein show that, mechanistically, SSA induces hematopoietic and lymphoid recovery by functionally enhancing both HSC self-renewal and propensity for lymphoid differentiation through intrinsic molecular changes. Our transcriptome analysis revealed further hematopoietic support through rejuvenation of the bone marrow (BM) microenvironment, with upregulation of key hematopoietic factors and master regulatory factors associated with aging such as Foxo1. These studies provide important cellular and molecular insights into understanding how SSA-induced regeneration of the hematopoietic compartment can underpin recovery of the immune system following damaging cytoablative treatments. These findings support a short-term strategy for clinical use of SSA to enhance the production of lymphoid cells and HSC engraftment, leading to improved outcomes in adult patients undergoing HSCT and immune depletion in general. © 2015 The Authors.
Keywords: controlled study; nonhuman; flow cytometry; t lymphocyte; animal cell; mouse; gene expression; bone marrow; erythroid precursor cell; animal experiment; hematopoietic stem cell transplantation; cell renewal; cell differentiation; b lymphocyte; whole body radiation; regulatory mechanism; upregulation; hematopoietic stem cell; sex hormone; sex steroid ablation; leukocyte; ablation therapy; transcription factor fkhr; chemokine receptor cxcr4; very late activation antigen 5; very late activation antigen 4; male; priority journal; article
Journal Title: Stem Cell Reports
Volume: 4
Issue: 3
ISSN: 2213-6711
Publisher: Cell Press  
Date Published: 2015-03-10
Start Page: 445
End Page: 458
Language: English
DOI: 10.1016/j.stemcr.2015.01.018
PROVIDER: scopus
PMCID: PMC4375937
PUBMED: 25733018
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84924586009&partnerID=40&md5=8d1f6600e06043eddcd915cb8774a581
Notes: Export Date: 2 April 2015 -- Source: Scopus
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Jarrod Andrew Dudakov
    58 Dudakov
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