Estrogen Regulates the Satellite Cell Compartment in Females

Brittany C. Collins, Robert W. Arpke, Alexie A. Larson, Cory W Baumann, Ning Xie, Christine A. Cabelka, Nardina L. Nash, Hanna Kaarina Juppi, Eija K. Laakkonen, Sarianna Sipilä, Vuokko Kovanen, Espen E. Spangenburg, Michael Kyba, Dawn A Lowe

Research output: Contribution to journalArticle

Abstract

Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing a greater deterioration in females around the time estrogen levels decrease at menopause. Here, we show that estrogen deficiency severely compromises the maintenance of muscle stem cells (i.e., satellite cells) as well as impairs self-renewal and differentiation into muscle fibers. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptor α and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri- to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females. Collins et al. show the loss of estrogen in female mice and post-menopausal women leads to a decrease in skeletal muscle stem cells. Using muscle stem cell-specific mutants, it was demonstrated that ERα is necessary for satellite cell maintenance, self-renewal, and protection from apoptosis, thereby promoting optimal muscle regeneration.

Original languageEnglish (US)
Pages (from-to)368-381.e6
JournalCell Reports
Volume28
Issue number2
DOIs
StatePublished - Jul 9 2019

Fingerprint

Muscle
Estrogens
Muscle Cells
Satellites
Stem Cells
Maintenance
Stem cells
Estrogen Receptors
Regeneration
Estradiol
Skeletal Muscle
Apoptosis
Postmenopause
Selective Estrogen Receptor Modulators
Muscles
Muscle Strength
Menopause
Biopsy
Hormones
Deterioration

Keywords

  • estradiol
  • muscle stem cells
  • ovarian hormones
  • quiescence
  • skeletal muscle

Cite this

Collins, B. C., Arpke, R. W., Larson, A. A., Baumann, C. W., Xie, N., Cabelka, C. A., ... Lowe, D. A. (2019). Estrogen Regulates the Satellite Cell Compartment in Females. Cell Reports, 28(2), 368-381.e6. https://doi.org/10.1016/j.celrep.2019.06.025

Estrogen Regulates the Satellite Cell Compartment in Females. / Collins, Brittany C.; Arpke, Robert W.; Larson, Alexie A.; Baumann, Cory W; Xie, Ning; Cabelka, Christine A.; Nash, Nardina L.; Juppi, Hanna Kaarina; Laakkonen, Eija K.; Sipilä, Sarianna; Kovanen, Vuokko; Spangenburg, Espen E.; Kyba, Michael; Lowe, Dawn A.

In: Cell Reports, Vol. 28, No. 2, 09.07.2019, p. 368-381.e6.

Research output: Contribution to journalArticle

Collins, BC, Arpke, RW, Larson, AA, Baumann, CW, Xie, N, Cabelka, CA, Nash, NL, Juppi, HK, Laakkonen, EK, Sipilä, S, Kovanen, V, Spangenburg, EE, Kyba, M & Lowe, DA 2019, 'Estrogen Regulates the Satellite Cell Compartment in Females', Cell Reports, vol. 28, no. 2, pp. 368-381.e6. https://doi.org/10.1016/j.celrep.2019.06.025
Collins BC, Arpke RW, Larson AA, Baumann CW, Xie N, Cabelka CA et al. Estrogen Regulates the Satellite Cell Compartment in Females. Cell Reports. 2019 Jul 9;28(2):368-381.e6. https://doi.org/10.1016/j.celrep.2019.06.025
Collins, Brittany C. ; Arpke, Robert W. ; Larson, Alexie A. ; Baumann, Cory W ; Xie, Ning ; Cabelka, Christine A. ; Nash, Nardina L. ; Juppi, Hanna Kaarina ; Laakkonen, Eija K. ; Sipilä, Sarianna ; Kovanen, Vuokko ; Spangenburg, Espen E. ; Kyba, Michael ; Lowe, Dawn A. / Estrogen Regulates the Satellite Cell Compartment in Females. In: Cell Reports. 2019 ; Vol. 28, No. 2. pp. 368-381.e6.
@article{61498b203ea34cd08c462f1bf3acaabe,
title = "Estrogen Regulates the Satellite Cell Compartment in Females",
abstract = "Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing a greater deterioration in females around the time estrogen levels decrease at menopause. Here, we show that estrogen deficiency severely compromises the maintenance of muscle stem cells (i.e., satellite cells) as well as impairs self-renewal and differentiation into muscle fibers. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptor α and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri- to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females. Collins et al. show the loss of estrogen in female mice and post-menopausal women leads to a decrease in skeletal muscle stem cells. Using muscle stem cell-specific mutants, it was demonstrated that ERα is necessary for satellite cell maintenance, self-renewal, and protection from apoptosis, thereby promoting optimal muscle regeneration.",
keywords = "estradiol, muscle stem cells, ovarian hormones, quiescence, skeletal muscle",
author = "Collins, {Brittany C.} and Arpke, {Robert W.} and Larson, {Alexie A.} and Baumann, {Cory W} and Ning Xie and Cabelka, {Christine A.} and Nash, {Nardina L.} and Juppi, {Hanna Kaarina} and Laakkonen, {Eija K.} and Sarianna Sipil{\"a} and Vuokko Kovanen and Spangenburg, {Espen E.} and Michael Kyba and Lowe, {Dawn A}",
year = "2019",
month = "7",
day = "9",
doi = "10.1016/j.celrep.2019.06.025",
language = "English (US)",
volume = "28",
pages = "368--381.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Estrogen Regulates the Satellite Cell Compartment in Females

AU - Collins, Brittany C.

AU - Arpke, Robert W.

AU - Larson, Alexie A.

AU - Baumann, Cory W

AU - Xie, Ning

AU - Cabelka, Christine A.

AU - Nash, Nardina L.

AU - Juppi, Hanna Kaarina

AU - Laakkonen, Eija K.

AU - Sipilä, Sarianna

AU - Kovanen, Vuokko

AU - Spangenburg, Espen E.

AU - Kyba, Michael

AU - Lowe, Dawn A

PY - 2019/7/9

Y1 - 2019/7/9

N2 - Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing a greater deterioration in females around the time estrogen levels decrease at menopause. Here, we show that estrogen deficiency severely compromises the maintenance of muscle stem cells (i.e., satellite cells) as well as impairs self-renewal and differentiation into muscle fibers. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptor α and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri- to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females. Collins et al. show the loss of estrogen in female mice and post-menopausal women leads to a decrease in skeletal muscle stem cells. Using muscle stem cell-specific mutants, it was demonstrated that ERα is necessary for satellite cell maintenance, self-renewal, and protection from apoptosis, thereby promoting optimal muscle regeneration.

AB - Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing a greater deterioration in females around the time estrogen levels decrease at menopause. Here, we show that estrogen deficiency severely compromises the maintenance of muscle stem cells (i.e., satellite cells) as well as impairs self-renewal and differentiation into muscle fibers. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptor α and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri- to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females. Collins et al. show the loss of estrogen in female mice and post-menopausal women leads to a decrease in skeletal muscle stem cells. Using muscle stem cell-specific mutants, it was demonstrated that ERα is necessary for satellite cell maintenance, self-renewal, and protection from apoptosis, thereby promoting optimal muscle regeneration.

KW - estradiol

KW - muscle stem cells

KW - ovarian hormones

KW - quiescence

KW - skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=85068113718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068113718&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2019.06.025

DO - 10.1016/j.celrep.2019.06.025

M3 - Article

VL - 28

SP - 368-381.e6

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 2

ER -