Cardiac transcription factors driven lineage-specification of adult stem cells.
Differentiation of human bone marrow mesenchymal stem cells (hBMSC) into the cardiac lineage has been assayed using different approaches such as coculture with cardiac or embryonic cells, treatment with factors, or by seeding cells in organotypic cultures. In most cases, differentiation was evaluated in terms of expression of cardiac-specific markers at protein or molecular level, electrophysiological properties, and formation of sarcomers in differentiated cells. As observed in embryonic stem cells and cardiac progenitors, differentiation of MSC towards the cardiac lineage was preceded by translocation of NKX2.5 and GATA4 transcription factors to the nucleus. Here, we induce differentiation of hBMSC towards the cardiac lineage using coculture with neonatal rat cardiomyocytes. Although important ultrastructural changes occurred during the course of differentiation, sarcomerogenesis was not fully achieved even after long periods of time. Nevertheless, we show that the main cardiac markers, NKX2.5 and GATA4, translocate to the nucleus in a process characteristic of cardiac specification.
Armiñán
Ana
A
Centro de Investigación Príncipe Felipe, Valencia, Spain.
Gandía
Carolina
C
García-Verdugo
José Manuel
JM
Lledó
Elisa
E
Mullor
José Luis
JL
Montero
José Anastasio
JA
Sepúlveda
Pilar
P
D000199:Actins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning; D024722:Cardiac Myosins; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D050991:GATA4 Transcription Factor / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D019210:Troponin I / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C501641:MYH7 protein, human; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D019210:Troponin I; D009320:Atrial Natriuretic Factor; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains