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

doi:10.1016/j.celrep.2019.06.025

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 journal › Article › peer-review

10 Scopus citations

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 language	English (US)
Pages (from-to)	368-381.e6
Journal	Cell reports
Volume	28
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2019.06.025
State	Published - Jul 9 2019

Bibliographical note

Funding Information:
We thank Angus Lindsay, Vineesha Kollipara, Tara Mader, Mayank Verma, Alessandro Magli, Yi Ren, and Olivia Recht for technical assistance and Atsushi Asakura and Ken Korach/Andrea Hevener for the Pax7 CreERT2/+ ;R26R tdTomato mice and ERα floxed mice, respectively. Bazedoxifene was a gift from Pfizer. We thank the University of Minnesota Genomics Center for providing sequencing series for this paper. We thank Cynthia S. Faraday for graphic design. Our research has been supported by the NIH grants R01-AG031743 (D.A.L.), R01-AR055685 (M.K.), T32-AR007612 (B.C.C., R.W.A., C.W.B., and C.A.C.), and T32-AG0299796 (A.A.L.); the Muscular Dystrophy Association grant MDA351022 (M.K.); a grant from the American Diabetes Association BS-1-15-170 (E.E.S.); a grant from the Office of the Vice President for Research, University of Minnesota (D.A.L.); and grants from the Academy of Finland 275323 (V.K.) and 309504 (E.K.L.). B.C.C. was also supported by a University of Minnesota Interdisciplinary Doctoral Fellowship .

Keywords

estradiol
muscle stem cells
ovarian hormones
quiescence
skeletal muscle

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Access

10.1016/j.celrep.2019.06.025

Fingerprint Dive into the research topics of 'Estrogen Regulates the Satellite Cell Compartment in Females'. Together they form a unique fingerprint.

Cite this

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 journal › Article › peer-review

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}",

note = "Funding Information: We thank Angus Lindsay, Vineesha Kollipara, Tara Mader, Mayank Verma, Alessandro Magli, Yi Ren, and Olivia Recht for technical assistance and Atsushi Asakura and Ken Korach/Andrea Hevener for the Pax7 CreERT2/+ ;R26R tdTomato mice and ERα floxed mice, respectively. Bazedoxifene was a gift from Pfizer. We thank the University of Minnesota Genomics Center for providing sequencing series for this paper. We thank Cynthia S. Faraday for graphic design. Our research has been supported by the NIH grants R01-AG031743 (D.A.L.), R01-AR055685 (M.K.), T32-AR007612 (B.C.C., R.W.A., C.W.B., and C.A.C.), and T32-AG0299796 (A.A.L.); the Muscular Dystrophy Association grant MDA351022 (M.K.); a grant from the American Diabetes Association BS-1-15-170 (E.E.S.); a grant from the Office of the Vice President for Research, University of Minnesota (D.A.L.); and grants from the Academy of Finland 275323 (V.K.) and 309504 (E.K.L.). B.C.C. was also supported by a University of Minnesota Interdisciplinary Doctoral Fellowship . ",

year = "2019",

month = jul,

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

N1 - Funding Information: We thank Angus Lindsay, Vineesha Kollipara, Tara Mader, Mayank Verma, Alessandro Magli, Yi Ren, and Olivia Recht for technical assistance and Atsushi Asakura and Ken Korach/Andrea Hevener for the Pax7 CreERT2/+ ;R26R tdTomato mice and ERα floxed mice, respectively. Bazedoxifene was a gift from Pfizer. We thank the University of Minnesota Genomics Center for providing sequencing series for this paper. We thank Cynthia S. Faraday for graphic design. Our research has been supported by the NIH grants R01-AG031743 (D.A.L.), R01-AR055685 (M.K.), T32-AR007612 (B.C.C., R.W.A., C.W.B., and C.A.C.), and T32-AG0299796 (A.A.L.); the Muscular Dystrophy Association grant MDA351022 (M.K.); a grant from the American Diabetes Association BS-1-15-170 (E.E.S.); a grant from the Office of the Vice President for Research, University of Minnesota (D.A.L.); and grants from the Academy of Finland 275323 (V.K.) and 309504 (E.K.L.). B.C.C. was also supported by a University of Minnesota Interdisciplinary Doctoral Fellowship .

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

C2 - 31291574

AN - SCOPUS:85068113718

VL - 28

SP - 368-381.e6

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 2

ER -