Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis

M. K. Nanjappa, T. I. Medrano, G. S. Prins, Haolin Chen, Barry R Zirkin, P. S. Cooke

Research output: Contribution to journalArticle

Abstract

Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete testosterone required for male sexual differentiation, spermatogenesis, and fertility, were recently identified in rat testes. Various types of stem cells have shown the ability to differentiate into other tissues, but there is no information on the plasticity of adult rat SLCs (rSLCs). This study investigated the ability of rSLCs to transdifferentiate into cell types from all three germ layers—prostatic epithelium (endoderm), uterine epithelium (mesoderm), and epidermis (ectoderm)—under the influence of inductive mesenchyme from fetal and neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme from green fluorescent protein (GFP)-expressing mice was used. Tissue recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs grafted into adult male hosts formed ductal structures resembling prostate after 5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP expression, and expressed characteristic markers of prostatic epithelium. Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple columnar epithelium that was histologically similar to normal uterine epithelium and expressed typical uterine epithelial markers, but was of rSLC origin. In contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants, suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate into uterine and prostatic epithelium, mesodermal, and endodermal derivatives, respectively, but they may have a limited transdifferentiation potential, as shown by their inability to form epidermis, an ectodermal derivative.

Original languageEnglish (US)
Pages (from-to)1165-1173
Number of pages9
JournalAndrology
Volume5
Issue number6
DOIs
StatePublished - Nov 1 2017

Fingerprint

Leydig Cells
Epidermis
Stem Cells
Epithelium
Mesoderm
Prostate
Green Fluorescent Proteins
Sex Differentiation
Endoderm
Ectoderm
Cell Lineage
Spermatogenesis
Dermis
Fertility
Testosterone
Testis
Fetus

Keywords

  • cell plasticity
  • ectoderm
  • endoderm
  • mesoderm
  • pluripotent
  • tissue recombination

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Reproductive Medicine
  • Endocrinology
  • Urology

Cite this

Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis. / Nanjappa, M. K.; Medrano, T. I.; Prins, G. S.; Chen, Haolin; Zirkin, Barry R; Cooke, P. S.

In: Andrology, Vol. 5, No. 6, 01.11.2017, p. 1165-1173.

Research output: Contribution to journalArticle

Nanjappa, M. K. ; Medrano, T. I. ; Prins, G. S. ; Chen, Haolin ; Zirkin, Barry R ; Cooke, P. S. / Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis. In: Andrology. 2017 ; Vol. 5, No. 6. pp. 1165-1173.
@article{62c67722a4a2415bae1efb278762d8e0,
title = "Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis",
abstract = "Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete testosterone required for male sexual differentiation, spermatogenesis, and fertility, were recently identified in rat testes. Various types of stem cells have shown the ability to differentiate into other tissues, but there is no information on the plasticity of adult rat SLCs (rSLCs). This study investigated the ability of rSLCs to transdifferentiate into cell types from all three germ layers—prostatic epithelium (endoderm), uterine epithelium (mesoderm), and epidermis (ectoderm)—under the influence of inductive mesenchyme from fetal and neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme from green fluorescent protein (GFP)-expressing mice was used. Tissue recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs grafted into adult male hosts formed ductal structures resembling prostate after 5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP expression, and expressed characteristic markers of prostatic epithelium. Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple columnar epithelium that was histologically similar to normal uterine epithelium and expressed typical uterine epithelial markers, but was of rSLC origin. In contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants, suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate into uterine and prostatic epithelium, mesodermal, and endodermal derivatives, respectively, but they may have a limited transdifferentiation potential, as shown by their inability to form epidermis, an ectodermal derivative.",
keywords = "cell plasticity, ectoderm, endoderm, mesoderm, pluripotent, tissue recombination",
author = "Nanjappa, {M. K.} and Medrano, {T. I.} and Prins, {G. S.} and Haolin Chen and Zirkin, {Barry R} and Cooke, {P. S.}",
year = "2017",
month = "11",
day = "1",
doi = "10.1111/andr.12415",
language = "English (US)",
volume = "5",
pages = "1165--1173",
journal = "Andrology",
issn = "2047-2919",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis

AU - Nanjappa, M. K.

AU - Medrano, T. I.

AU - Prins, G. S.

AU - Chen, Haolin

AU - Zirkin, Barry R

AU - Cooke, P. S.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete testosterone required for male sexual differentiation, spermatogenesis, and fertility, were recently identified in rat testes. Various types of stem cells have shown the ability to differentiate into other tissues, but there is no information on the plasticity of adult rat SLCs (rSLCs). This study investigated the ability of rSLCs to transdifferentiate into cell types from all three germ layers—prostatic epithelium (endoderm), uterine epithelium (mesoderm), and epidermis (ectoderm)—under the influence of inductive mesenchyme from fetal and neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme from green fluorescent protein (GFP)-expressing mice was used. Tissue recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs grafted into adult male hosts formed ductal structures resembling prostate after 5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP expression, and expressed characteristic markers of prostatic epithelium. Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple columnar epithelium that was histologically similar to normal uterine epithelium and expressed typical uterine epithelial markers, but was of rSLC origin. In contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants, suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate into uterine and prostatic epithelium, mesodermal, and endodermal derivatives, respectively, but they may have a limited transdifferentiation potential, as shown by their inability to form epidermis, an ectodermal derivative.

AB - Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete testosterone required for male sexual differentiation, spermatogenesis, and fertility, were recently identified in rat testes. Various types of stem cells have shown the ability to differentiate into other tissues, but there is no information on the plasticity of adult rat SLCs (rSLCs). This study investigated the ability of rSLCs to transdifferentiate into cell types from all three germ layers—prostatic epithelium (endoderm), uterine epithelium (mesoderm), and epidermis (ectoderm)—under the influence of inductive mesenchyme from fetal and neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme from green fluorescent protein (GFP)-expressing mice was used. Tissue recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs grafted into adult male hosts formed ductal structures resembling prostate after 5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP expression, and expressed characteristic markers of prostatic epithelium. Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple columnar epithelium that was histologically similar to normal uterine epithelium and expressed typical uterine epithelial markers, but was of rSLC origin. In contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants, suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate into uterine and prostatic epithelium, mesodermal, and endodermal derivatives, respectively, but they may have a limited transdifferentiation potential, as shown by their inability to form epidermis, an ectodermal derivative.

KW - cell plasticity

KW - ectoderm

KW - endoderm

KW - mesoderm

KW - pluripotent

KW - tissue recombination

UR - http://www.scopus.com/inward/record.url?scp=85032288202&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032288202&partnerID=8YFLogxK

U2 - 10.1111/andr.12415

DO - 10.1111/andr.12415

M3 - Article

C2 - 29073338

AN - SCOPUS:85032288202

VL - 5

SP - 1165

EP - 1173

JO - Andrology

JF - Andrology

SN - 2047-2919

IS - 6

ER -