title: N-Cadherin is a prospective cell surface marker of human mesenchymal stem cells that have high ability for cardiomyocyte differentiation.
abstract: Mesenchymal stem cells (MSCs) are among the most promising sources of stem cells for regenerative medicine. However, the range of their differentiation ability is very limited. In this study, we explored prospective cell surface markers of human MSCs that readily differentiate into cardiomyocytes. When the cardiomyogenic differentiation potential and the expression of cell surface markers involved in heart development were analyzed using various immortalized human MSC lines, the MSCs with high expression of N-cadherin showed a higher probability of differentiation into beating cardiomyocytes. The differentiated cardiomyocytes expressed terminally differentiated cardiomyocyte-specific markers such as α-actinin, cardiac troponin T, and connexin-43. A similar correlation was observed with primary human MSCs derived from bone marrow and adipose tissue. Moreover, N-cadherin-positive MSCs isolated with N-cadherin antibody-conjugated magnetic beads showed an apparently higher ability to differentiate into cardiomyocytes than the N-cadherin-negative population. Quantitative polymerase chain reaction analyses demonstrated that the N-cadherin-positive population expressed significantly elevated levels of cardiomyogenic progenitor-specific transcription factors, including Nkx2.5, Hand1, and GATA4 mRNAs. Our results suggest that N-cadherin is a novel prospective cell surface marker of human MSCs that show a better ability for cardiomyocyte differentiation.
authors.affiliation: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Ishimine
authors.forename: Norio
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Mari
authors.initials: M
authors.lastname: Sasao
authors.forename: Mika
authors.initials: M
authors.lastname: Tadokoro
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kami
authors.forename: Shinji
authors.initials: S
authors.lastname: Komazaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Tokuhara
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takada
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ito
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kuno
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohgushi
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.forename: Akira
authors.initials: A
authors.lastname: Kurisaki
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D050991:GATA4 Transcription Factor / Q000235:genetics; D015870:Gene Expression; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C484170:GATA4 protein, human; C095552:NKX2-5 protein, human; C097341:helix-loop-helix protein, eHAND
keywords: Cardiomyocyte; Flk-1; Mesenchymal stem cells; N-cadherin; c-Kit