Characterization and isolation of stem cell-enriched human hair follicle bulge cells

Manabu Ohyama, Atsushi Terunuma, Christine L. Tock, Michael F. Radonovich, Cynthia A. Pise-Masison, Steven B. Hopping, John N. Brady, Mark C. Udey, Jonathan C. Vogel

Research output: Contribution to journalArticle

443 Citations (Scopus)

Abstract

The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24 loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.

Original languageEnglish
Pages (from-to)249-260
Number of pages12
JournalJournal of Clinical Investigation
Volume116
Issue number1
DOIs
Publication statusPublished - 2006 Jan

Fingerprint

Hair Follicle
Stem Cells
Keratinocytes
Follistatin
Laser Capture Microdissection
Stem Cell Niche
Activins
Oligonucleotide Array Sequence Analysis
Transcriptome
Genetic Therapy
Hair
Genes
Cell Biology
Regeneration
Suspensions
Cell Proliferation
Bone and Bones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ohyama, M., Terunuma, A., Tock, C. L., Radonovich, M. F., Pise-Masison, C. A., Hopping, S. B., ... Vogel, J. C. (2006). Characterization and isolation of stem cell-enriched human hair follicle bulge cells. Journal of Clinical Investigation, 116(1), 249-260. https://doi.org/10.1172/JCI26043

Characterization and isolation of stem cell-enriched human hair follicle bulge cells. / Ohyama, Manabu; Terunuma, Atsushi; Tock, Christine L.; Radonovich, Michael F.; Pise-Masison, Cynthia A.; Hopping, Steven B.; Brady, John N.; Udey, Mark C.; Vogel, Jonathan C.

In: Journal of Clinical Investigation, Vol. 116, No. 1, 01.2006, p. 249-260.

Research output: Contribution to journalArticle

Ohyama, M, Terunuma, A, Tock, CL, Radonovich, MF, Pise-Masison, CA, Hopping, SB, Brady, JN, Udey, MC & Vogel, JC 2006, 'Characterization and isolation of stem cell-enriched human hair follicle bulge cells', Journal of Clinical Investigation, vol. 116, no. 1, pp. 249-260. https://doi.org/10.1172/JCI26043
Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB et al. Characterization and isolation of stem cell-enriched human hair follicle bulge cells. Journal of Clinical Investigation. 2006 Jan;116(1):249-260. https://doi.org/10.1172/JCI26043
Ohyama, Manabu ; Terunuma, Atsushi ; Tock, Christine L. ; Radonovich, Michael F. ; Pise-Masison, Cynthia A. ; Hopping, Steven B. ; Brady, John N. ; Udey, Mark C. ; Vogel, Jonathan C. / Characterization and isolation of stem cell-enriched human hair follicle bulge cells. In: Journal of Clinical Investigation. 2006 ; Vol. 116, No. 1. pp. 249-260.
@article{59b6ca0ba12a483890799189bf7d5e04,
title = "Characterization and isolation of stem cell-enriched human hair follicle bulge cells",
abstract = "The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24 loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.",
author = "Manabu Ohyama and Atsushi Terunuma and Tock, {Christine L.} and Radonovich, {Michael F.} and Pise-Masison, {Cynthia A.} and Hopping, {Steven B.} and Brady, {John N.} and Udey, {Mark C.} and Vogel, {Jonathan C.}",
year = "2006",
month = "1",
doi = "10.1172/JCI26043",
language = "English",
volume = "116",
pages = "249--260",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

TY - JOUR

T1 - Characterization and isolation of stem cell-enriched human hair follicle bulge cells

AU - Ohyama, Manabu

AU - Terunuma, Atsushi

AU - Tock, Christine L.

AU - Radonovich, Michael F.

AU - Pise-Masison, Cynthia A.

AU - Hopping, Steven B.

AU - Brady, John N.

AU - Udey, Mark C.

AU - Vogel, Jonathan C.

PY - 2006/1

Y1 - 2006/1

N2 - The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24 loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.

AB - The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24 loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.

UR - http://www.scopus.com/inward/record.url?scp=31044431832&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31044431832&partnerID=8YFLogxK

U2 - 10.1172/JCI26043

DO - 10.1172/JCI26043

M3 - Article

VL - 116

SP - 249

EP - 260

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -