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

Danika M Khong; Jarrod A Dudakov; Maree V Hammett; Marc I Jurblum; Sacha M L Khong; Gabrielle L Goldberg; Tomoo Ueno; Lisa G Spyroglou; Lauren Florence Young; Marcel R M van den Brink; Richard L Boyd; Ann P Chidgey

doi:10.1016/j.stemcr.2015.01.018

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

Danika M Khong, Jarrod A Dudakov, Maree V Hammett, Marc I Jurblum, Sacha M L Khong, Gabrielle L Goldberg, Tomoo Ueno, Lisa G Spyroglou, Lauren Florence Young, Marcel R M van den Brink, Richard L Boyd, Ann P Chidgey

Anatomy & Developmental Biology

Research output: Contribution to journal › Article › Research › peer-review

28 Citations (Scopus)

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.

Original language	English
Pages (from-to)	445 - 458
Number of pages	14
Journal	Stem Cell Reports
Volume	4
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2015.01.018
Publication status	Published - 2015

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Khong, D. M., Dudakov, J. A., Hammett, M. V., Jurblum, M. I., Khong, S. M. L., Goldberg, G. L., Ueno, T., Spyroglou, L. G., Young, L. F., van den Brink, M. R. M., Boyd, R. L., & Chidgey, A. P. (2015). Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade. Stem Cell Reports, 4(3), 445 - 458. https://doi.org/10.1016/j.stemcr.2015.01.018

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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.",

author = "Khong, {Danika M} and Dudakov, {Jarrod A} and Hammett, {Maree V} and Jurblum, {Marc I} and Khong, {Sacha M L} and Goldberg, {Gabrielle L} and Tomoo Ueno and Spyroglou, {Lisa G} and Young, {Lauren Florence} and {van den Brink}, {Marcel R M} and Boyd, {Richard L} and Chidgey, {Ann P}",

year = "2015",

doi = "10.1016/j.stemcr.2015.01.018",

language = "English",

volume = "4",

pages = "445 -- 458",

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T1 - Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade

AU - Khong, Danika M

AU - Dudakov, Jarrod A

AU - Hammett, Maree V

AU - Jurblum, Marc I

AU - Khong, Sacha M L

AU - Goldberg, Gabrielle L

AU - Ueno, Tomoo

AU - Spyroglou, Lisa G

AU - Young, Lauren Florence

AU - van den Brink, Marcel R M

AU - Boyd, Richard L

AU - Chidgey, Ann P

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375937/pdf/main.pdf

U2 - 10.1016/j.stemcr.2015.01.018

DO - 10.1016/j.stemcr.2015.01.018

M3 - Article

SN - 2213-6711

VL - 4

SP - 445

EP - 458

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

ER -

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

Abstract

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