Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow

Min Hee Park, Hee Kyung Jin, Woo Kie Min, Won Woo Lee, Jeong Eun Lee, Haruhiko Akiyama, Herbert Herzog, Grigori N. Enikolopov, Edward H. Schuchman, Jae Sung Bae

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.

Original languageEnglish
Pages (from-to)1648-1660
Number of pages13
JournalEMBO Journal
Volume34
Issue number12
DOIs
StatePublished - 12 Jun 2015

Fingerprint

Stem Cell Niche
Neuropeptide Y
Hematopoietic Stem Cells
Stem cells
Bone
Bone Marrow
Sympathetic Nervous System
Neurology
Wounds and Injuries
Nervous System Trauma
Chemotherapy
Macrophages
Drug Therapy
Endothelial cells
Neuropeptides
Knockout Mice
Regeneration
Endothelial Cells
Cell Count
Pharmacology

Keywords

  • Bone marrow microenvironment
  • Hematopoietic stem cell
  • Neuropeptide Y
  • Regeneration
  • Sympathetic nervous system

Cite this

Park, Min Hee ; Jin, Hee Kyung ; Min, Woo Kie ; Lee, Won Woo ; Lee, Jeong Eun ; Akiyama, Haruhiko ; Herzog, Herbert ; Enikolopov, Grigori N. ; Schuchman, Edward H. ; Bae, Jae Sung. / Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow. In: EMBO Journal. 2015 ; Vol. 34, No. 12. pp. 1648-1660.
@article{9c0adcb1bea04a4ab01c89f47c8ad7f6,
title = "Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow",
abstract = "Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.",
keywords = "Bone marrow microenvironment, Hematopoietic stem cell, Neuropeptide Y, Regeneration, Sympathetic nervous system",
author = "Park, {Min Hee} and Jin, {Hee Kyung} and Min, {Woo Kie} and Lee, {Won Woo} and Lee, {Jeong Eun} and Haruhiko Akiyama and Herbert Herzog and Enikolopov, {Grigori N.} and Schuchman, {Edward H.} and Bae, {Jae Sung}",
year = "2015",
month = "6",
day = "12",
doi = "10.15252/embj.201490174",
language = "English",
volume = "34",
pages = "1648--1660",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "12",

}

Park, MH, Jin, HK, Min, WK, Lee, WW, Lee, JE, Akiyama, H, Herzog, H, Enikolopov, GN, Schuchman, EH & Bae, JS 2015, 'Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow', EMBO Journal, vol. 34, no. 12, pp. 1648-1660. https://doi.org/10.15252/embj.201490174

Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow. / Park, Min Hee; Jin, Hee Kyung; Min, Woo Kie; Lee, Won Woo; Lee, Jeong Eun; Akiyama, Haruhiko; Herzog, Herbert; Enikolopov, Grigori N.; Schuchman, Edward H.; Bae, Jae Sung.

In: EMBO Journal, Vol. 34, No. 12, 12.06.2015, p. 1648-1660.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow

AU - Park, Min Hee

AU - Jin, Hee Kyung

AU - Min, Woo Kie

AU - Lee, Won Woo

AU - Lee, Jeong Eun

AU - Akiyama, Haruhiko

AU - Herzog, Herbert

AU - Enikolopov, Grigori N.

AU - Schuchman, Edward H.

AU - Bae, Jae Sung

PY - 2015/6/12

Y1 - 2015/6/12

N2 - Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.

AB - Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.

KW - Bone marrow microenvironment

KW - Hematopoietic stem cell

KW - Neuropeptide Y

KW - Regeneration

KW - Sympathetic nervous system

UR - http://www.scopus.com/inward/record.url?scp=84930872362&partnerID=8YFLogxK

U2 - 10.15252/embj.201490174

DO - 10.15252/embj.201490174

M3 - Article

C2 - 25916827

AN - SCOPUS:84930872362

VL - 34

SP - 1648

EP - 1660

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 12

ER -