Calcium Dependent CAMTA1 in Adult Stem Cell Commitment to a Myocardial Lineage

Abstract

The phenotype of somatic cells has recently been found to be reversible. Direct reprogramming of one cell type into another has been achieved with transduction and over expression of exogenous defined transcription factors emphasizing their role in specifying cell fate. To discover early and novel endogenous transcription factors that may have a role in adult-derived stem cell acquisition of a cardiomyocyte phenotype, mesenchymal stem cells from human and mouse bone marrow and rat liver were co-cultured with neonatal cardiomyocytes as an in vitro cardiogenic microenvironment. Cell-cell communications develop between the two cell types as early as 24 hrs in co-culture and are required for elaboration of a myocardial phenotype in the stem cells 8–16 days later. These intercellular communications are associated with novel Ca2+ oscillations in the stem cells that are synchronous with the Ca2+ transients in adjacent cardiomyocytes and are detected in the stem cells as early as 24–48 hrs in co-culture. Early and significant up-regulation of Ca2+-dependent effectors, CAMTA1 and RCAN1 ensues before a myocardial program is activated. CAMTA1 loss-of-function minimizes the activation of the cardiac gene program in the stem cells. While the expression of RCAN1 suggests involvement of the well-characterized calcineurin-NFAT pathway as a response to a Ca2+ signal, the CAMTA1 up-regulated expression as a response to such a signal in the stem cells was unknown. Cell-cell communications between the stem cells and adjacent cardiomyocytes induce Ca2+ signals that activate a myocardial gene program in the stem cells via a novel and early Ca2+-dependent intermediate, up-regulation of CAMTA1.

Integrator of Stress Responses Calmodulin Binding Transcription Activator 1 (Camta1) Regulates miR-212/miR-132 Expression and Insulin Secretion

“…Increase in intracellular Ca 2ϩ is intricately linked to the mechanisms that modulate insulin secretion from beta cells (45). In another context, expression of CAMTA1 has been shown to be up-regulated in cells exposed to increased intracellular Ca 2ϩ , and this has been associated with novel expression of cardiac transcription factors (46). However, transcription factors can often function as both transcriptional repressors and activators, depending on temporal or cell-specific settings, as is, in fact, the case for Nkx2-2 (19 -21, 47, 48).…”

Reconstruction and validation of a constraint‐based metabolic network model for bone marrow‐derived mesenchymal stem cells

“…The data of other cells (later passages) were NOT used in our work; GSE30807 data series : This includes microarray data of a normal early passage BMMSC sample, GSM764199, which IS used in this work. The data of other cell types (osteosarcoma U2OS cells) were NOT used here; GSE32171 data series : This includes three early passage BMMSC samples, GSM797497, GSM797498 and GSM797499, which ARE used in the present study. The data of other type s (human MSCs in cardiomyocyte co‐culture) were NOT used.…”

Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor

“…Although CAMTA1 is expressed predominantly in the brain, it also is expressed in the heart (7), and it has been reported that CAMTA1 is required for differentiation of adult stem cells into myocardial cells (23). We did not detect any overt cardiac abnormalities in mice with global deletion of CAMTA1.…”