Asset Details
Do you wish to reserve the book?
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
Do you wish to request the book?
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
2012
Overview
The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported previously that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells
in vitro
by the addition of Gata4, Mef2c and Tbx5 (GMT). Here we use genetic lineage tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells
in vivo
by local delivery of GMT after coronary ligation. Induced cardiomyocytes became binucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling.
In vivo
delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast-activating peptide, thymosin β4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes.
Previous work has shown that a combination of three transcription factors can directly reprogram cardiac fibroblasts into cardiomyocyte-like cell
in vitro
; now, the same authors demonstrate
in vivo
reprogramming of cardiac fibroblasts into induced cardiomyocytes.
Heart-tissue regeneration in mice
Having shown previously that a combination of three transcription factors can directly reprogram cardiac fibroblasts to cardiomyocyte-like cells — the cells that drive the heartbeat —
in vitro
, Deepak Srivastava and colleagues now take this approach
in vivo
. Using a retrovirus to deliver the transcription factors directly to the hearts of adult mice, they demonstrate the conversion of non-myocytes to induced cardiomyocytes. Heart function improved and the area of damaged tissue shrank. Delivery of the multifunctional peptide thymosin β4 — which activates cardiac fibroblasts — along with the cardiac reprogramming factors resulted in further reduction in scar area and improvement in cardiac function.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/80
/ Animals
/ Biological and medical sciences
/ Female
/ GATA4 Transcription Factor - genetics
/ GATA4 Transcription Factor - metabolism
/ Humanities and Social Sciences
/ Male
/ Mice
/ Myocardial Infarction - drug therapy
/ Myocardial Infarction - pathology
/ Myocardial Infarction - physiopathology
/ Myocardial Infarction - therapy
/ Myocytes, Cardiac - cytology
/ Myocytes, Cardiac - drug effects
/ Myocytes, Cardiac - metabolism
/ Myocytes, Cardiac - physiology
/ Myogenic Regulatory Factors - genetics
/ Myogenic Regulatory Factors - metabolism
/ Proteins
/ Regenerative Medicine - methods
/ Rodents
/ Science
/ T-Box Domain Proteins - genetics
