Pluripotent stem cells identified in multiple murine tissues

Jonathan C. Howell, Wei Hua Lee, Paul Morrison, Jin Zhong, Mervin Yoder, Edward Srour

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Pluripotential stem cells (PSCs) have been recently described in many tissues including skeletal muscle, brain, and bone marrow. However, the true nature of these cells is still unclear, and their precise definition has yet to be determined. We hypothesized that a common, rare population of PSCs with a broad tissue differentiation potential can be identified in multiple murine tissues and that these cells are capable of transdifferentiation into cells of different primordial germ layer origins in response to diverse microenvironmental cues. To examine this hypothesis, we isolated phenotypically defined cells from murine skeletal muscle and cultured these cells under different conditions tailored to promote differentiation into several cell types including myocytes. We report here that in conditions permissive for hematopoietic differentiation, muscle-derived CD45-Sca-1+c-kit- cells differentiated into cells expressing hematopoietic-specific mRNA; while in conditions promoting myogenic, neuronal, and adipocytic differentiation, cells morphologically typical of these cell types expressing tissue-specific markers were identified 9-14 days in culture. When CD45-Sca-1+c-kit- cells from muscle or bone marrow were transplanted intracerebellarly into Purkinje cell degenerative (pcd) mice, the behavior of these mice improved 28 days after transplantation relative to mice injected with vehicle alone, suggesting that these cells contributed to the appearance of functional neuronal cells that may have improved the ataxic condition characteristic of these mice. Phenotypic analysis of single cell suspensions prepared from brain, blood, and intestinal epithelium revealed the presence of CD45- Sca-1+c-kit- cells in varying degrees. These studies suggest that a phenotypically common, multipotent cell can be identified in different tissues and that this cell may representa universal pluripotent stem cell residing at different levels in multiple murine tissues.

Original languageEnglish
Pages (from-to)158-173
Number of pages16
JournalAnnals of the New York Academy of Sciences
Volume996
StatePublished - 2003

Fingerprint

Pluripotent Stem Cells
Stem cells
Tissue
Muscle
Brain
Bone
Muscle Cells
Cells
Stem Cells
Suspensions
Skeletal Muscle
Blood
Cell Transdifferentiation
Bone Marrow
Single-Cell Analysis
Germ Layers
Messenger RNA
Purkinje Cells
Intestinal Mucosa
Cues

Keywords

  • Plasticity
  • Pluripotent stem cells
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pluripotent stem cells identified in multiple murine tissues. / Howell, Jonathan C.; Lee, Wei Hua; Morrison, Paul; Zhong, Jin; Yoder, Mervin; Srour, Edward.

In: Annals of the New York Academy of Sciences, Vol. 996, 2003, p. 158-173.

Research output: Contribution to journalArticle

Howell, Jonathan C. ; Lee, Wei Hua ; Morrison, Paul ; Zhong, Jin ; Yoder, Mervin ; Srour, Edward. / Pluripotent stem cells identified in multiple murine tissues. In: Annals of the New York Academy of Sciences. 2003 ; Vol. 996. pp. 158-173.
@article{507bf57b7ffe4755a099f55f8051349b,
title = "Pluripotent stem cells identified in multiple murine tissues",
abstract = "Pluripotential stem cells (PSCs) have been recently described in many tissues including skeletal muscle, brain, and bone marrow. However, the true nature of these cells is still unclear, and their precise definition has yet to be determined. We hypothesized that a common, rare population of PSCs with a broad tissue differentiation potential can be identified in multiple murine tissues and that these cells are capable of transdifferentiation into cells of different primordial germ layer origins in response to diverse microenvironmental cues. To examine this hypothesis, we isolated phenotypically defined cells from murine skeletal muscle and cultured these cells under different conditions tailored to promote differentiation into several cell types including myocytes. We report here that in conditions permissive for hematopoietic differentiation, muscle-derived CD45-Sca-1+c-kit- cells differentiated into cells expressing hematopoietic-specific mRNA; while in conditions promoting myogenic, neuronal, and adipocytic differentiation, cells morphologically typical of these cell types expressing tissue-specific markers were identified 9-14 days in culture. When CD45-Sca-1+c-kit- cells from muscle or bone marrow were transplanted intracerebellarly into Purkinje cell degenerative (pcd) mice, the behavior of these mice improved 28 days after transplantation relative to mice injected with vehicle alone, suggesting that these cells contributed to the appearance of functional neuronal cells that may have improved the ataxic condition characteristic of these mice. Phenotypic analysis of single cell suspensions prepared from brain, blood, and intestinal epithelium revealed the presence of CD45- Sca-1+c-kit- cells in varying degrees. These studies suggest that a phenotypically common, multipotent cell can be identified in different tissues and that this cell may representa universal pluripotent stem cell residing at different levels in multiple murine tissues.",
keywords = "Plasticity, Pluripotent stem cells, Skeletal muscle",
author = "Howell, {Jonathan C.} and Lee, {Wei Hua} and Paul Morrison and Jin Zhong and Mervin Yoder and Edward Srour",
year = "2003",
language = "English",
volume = "996",
pages = "158--173",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Pluripotent stem cells identified in multiple murine tissues

AU - Howell, Jonathan C.

AU - Lee, Wei Hua

AU - Morrison, Paul

AU - Zhong, Jin

AU - Yoder, Mervin

AU - Srour, Edward

PY - 2003

Y1 - 2003

N2 - Pluripotential stem cells (PSCs) have been recently described in many tissues including skeletal muscle, brain, and bone marrow. However, the true nature of these cells is still unclear, and their precise definition has yet to be determined. We hypothesized that a common, rare population of PSCs with a broad tissue differentiation potential can be identified in multiple murine tissues and that these cells are capable of transdifferentiation into cells of different primordial germ layer origins in response to diverse microenvironmental cues. To examine this hypothesis, we isolated phenotypically defined cells from murine skeletal muscle and cultured these cells under different conditions tailored to promote differentiation into several cell types including myocytes. We report here that in conditions permissive for hematopoietic differentiation, muscle-derived CD45-Sca-1+c-kit- cells differentiated into cells expressing hematopoietic-specific mRNA; while in conditions promoting myogenic, neuronal, and adipocytic differentiation, cells morphologically typical of these cell types expressing tissue-specific markers were identified 9-14 days in culture. When CD45-Sca-1+c-kit- cells from muscle or bone marrow were transplanted intracerebellarly into Purkinje cell degenerative (pcd) mice, the behavior of these mice improved 28 days after transplantation relative to mice injected with vehicle alone, suggesting that these cells contributed to the appearance of functional neuronal cells that may have improved the ataxic condition characteristic of these mice. Phenotypic analysis of single cell suspensions prepared from brain, blood, and intestinal epithelium revealed the presence of CD45- Sca-1+c-kit- cells in varying degrees. These studies suggest that a phenotypically common, multipotent cell can be identified in different tissues and that this cell may representa universal pluripotent stem cell residing at different levels in multiple murine tissues.

AB - Pluripotential stem cells (PSCs) have been recently described in many tissues including skeletal muscle, brain, and bone marrow. However, the true nature of these cells is still unclear, and their precise definition has yet to be determined. We hypothesized that a common, rare population of PSCs with a broad tissue differentiation potential can be identified in multiple murine tissues and that these cells are capable of transdifferentiation into cells of different primordial germ layer origins in response to diverse microenvironmental cues. To examine this hypothesis, we isolated phenotypically defined cells from murine skeletal muscle and cultured these cells under different conditions tailored to promote differentiation into several cell types including myocytes. We report here that in conditions permissive for hematopoietic differentiation, muscle-derived CD45-Sca-1+c-kit- cells differentiated into cells expressing hematopoietic-specific mRNA; while in conditions promoting myogenic, neuronal, and adipocytic differentiation, cells morphologically typical of these cell types expressing tissue-specific markers were identified 9-14 days in culture. When CD45-Sca-1+c-kit- cells from muscle or bone marrow were transplanted intracerebellarly into Purkinje cell degenerative (pcd) mice, the behavior of these mice improved 28 days after transplantation relative to mice injected with vehicle alone, suggesting that these cells contributed to the appearance of functional neuronal cells that may have improved the ataxic condition characteristic of these mice. Phenotypic analysis of single cell suspensions prepared from brain, blood, and intestinal epithelium revealed the presence of CD45- Sca-1+c-kit- cells in varying degrees. These studies suggest that a phenotypically common, multipotent cell can be identified in different tissues and that this cell may representa universal pluripotent stem cell residing at different levels in multiple murine tissues.

KW - Plasticity

KW - Pluripotent stem cells

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=0038129696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038129696&partnerID=8YFLogxK

M3 - Article

C2 - 12799294

AN - SCOPUS:0038129696

VL - 996

SP - 158

EP - 173

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -