scholarly journals Induced in vivo transdifferentiation of vertebrate muscle into early endoderm-like cells

2020 ◽  
Author(s):  
P. Duc Dong ◽  
Joseph Lancman ◽  
Clyde Campbell ◽  
Raquel Espin-Palazon ◽  
Jonatan Matalonga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Cell Lineage ◽  
Muscle Gene Expression ◽  
Functional Studies ◽  
Differentiated Cells ◽  
Pluripotency Gene ◽  
Fundamental Insight ◽  
Muscle Gene

Abstract The extent to which differentiated cells, while remaining in their native microenvironment, can be reprogrammed to assume a different identity will reveal fundamental insight into cellular plasticity and impact regenerative medicine. To investigate in vivo cell lineage potential, we leveraged the zebrafish as a practical vertebrate platform to determine factors and mechanisms necessary to induce differentiated cells of one germ layer to adopt the lineage of another. We discovered that ectopic co-expression of Sox32 and Oct4 in several non-endoderm lineages, including skeletal muscle, can specifically trigger an early endoderm genetic program in a cell-autonomous manner. Gene expression, live imaging, and functional studies reveal that the endoderm-induced muscle cells lose muscle gene expression and morphology, while specifically gaining endoderm organogenesis lineage markers, such as the pancreatic specification genes, hhex and ptf1a, via a mechanism resembling normal development. Endoderm induction by a pluripotent defective form of Oct4, endoderm markers appearing prior to loss of muscle cell morphology, and a lack of mesoderm, ectoderm, dedifferentiation, and pluripotency gene activation, together, suggests that reprogramming is endoderm specific and occurs via direct transdifferentiation. Our work demonstrates that within a living vertebrate animal, differentiated cells can be induced to directly adopt the identity of a completely unrelated cell lineage, while remaining in a distinct microenvironment, suggesting that differentiated cells in vivo may be more amenable to lineage conversion than previously appreciated. This discovery of extensive lineage potential of differentiated cells, in vivo, challenges our understanding of cell lineage restriction and may pave the way towards new in vivo sources of replacement cells for degenerative diseases such as diabetes.

scholarly journals In vivo lineage conversion of vertebrate muscle into early endoderm-like cells

2019 ◽  
Author(s):  
Clyde Campbell ◽  
Joseph J. Lancman ◽  
Raquel Espin Palazon ◽  
Jonatan Matalonga ◽  
Jiaye He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Cell Lineage ◽  
Muscle Gene Expression ◽  
Functional Studies ◽  
Differentiated Cells ◽  
Pluripotency Gene ◽  
Fundamental Insight ◽  
Muscle Gene

The extent to which differentiated cells, while remaining in their native microenvironment, can be reprogrammed to assume a different identity will reveal fundamental insight into cellular plasticity and impact regenerative medicine. To investigate in vivo cell lineage potential, we leveraged the zebrafish as a practical vertebrate platform to determine factors and mechanisms necessary to induce differentiated cells of one germ layer to adopt the lineage of another. We discovered that ectopic co-expression of Sox32 and Oct4 in several non-endoderm lineages, including skeletal muscle, can specifically trigger an early endoderm genetic program in a cell-autonomous manner. Gene expression, live imaging, and functional studies reveal that the endoderm-induced muscle cells lose muscle gene expression and morphology, while specifically gaining endoderm organogenesis markers, such as the pancreatic specification genes, hhex and ptf1a, via a mechanism resembling normal development. Endoderm induction by a pluripotent defective form of Oct4, endoderm markers appearing prior to loss of muscle cell morphology, a lack of dependence on cell division, and a lack of mesoderm, ectoderm, dedifferentiation, and pluripotency gene activation, together, suggests that reprogramming is endoderm specific and occurs via direct lineage conversion. Our work demonstrates that within a vertebrate animal, stably differentiated cells can be induced to directly adopt the identity of a completely unrelated cell lineage, while remaining in a distinct microenvironment, suggesting that differentiated cells in vivo may be more amenable to lineage conversion than previously appreciated. This discovery of possibly unlimited lineage potential of differentiated cells in vivo challenges our understanding of cell lineage restriction and may pave the way towards a vast new in vivo supply of replacement cells for degenerative diseases such as diabetes.

scholarly journals Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245618
Author(s):  
Abhinav Adhikari ◽  
William Kim ◽  
Judith Davie
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Gene Activation ◽  
Gene Promoters ◽  
Muscle Gene Expression ◽  
Transcription Machinery ◽  
Muscle Genes ◽  
Muscle Gene

Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors.

Epigenetic effects induced by the ectopic expression of Pax7 in 3T3-L1

2021 ◽  
Author(s):  
Alaa Elgaabari ◽  
Atsuko Miyawaki-Kuwakado ◽  
Kosuke Tomimatsu ◽  
Qianmei Wu ◽  
Kosuke Tokunaga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Ectopic Expression ◽  
Histone Mark ◽  
Differentiation Potential ◽  
Muscle Gene Expression ◽  
Repressive Histone Mark ◽  
Myogenic Factor ◽  
Muscle Gene

Abstract Although skeletal muscle cells and adipocytes are derived from the same mesoderm, they do not transdifferentiate in vivo and are strictly distinct at the level of gene expression. To elucidate some of the regulatory mechanisms underlying this strict distinction, Pax7, a myogenic factor, was ectopically expressed in 3T3-L1 adipose progenitor cells to perturb their adipocyte differentiation potential. Transcriptome analysis showed that ectopic expression of Pax7 repressed the expression of some adipocyte genes and induced expression of some skeletal muscle cell genes. We next profiled the epigenomic state altered by Pax7 expression using H3K27ac, an activating histone mark, and H3K27me3, a repressive histone mark, as indicators. Our results show that ectopic expression of Pax7 did not result in the formation of H3K27ac at loci of skeletal muscle-related genes, but instead resulted in the formation of H3K27me3 at adipocyte-related gene loci. These findings suggest that the primary function of ectopic Pax7 expression is the formation of H3K27me3, and muscle gene expression results from secondary regulation.

scholarly journals Modulation of Smooth Muscle Gene Expression by Association of Histone Acetyltransferases and Deacetylases with Myocardin

2005 ◽  
Vol 25 (1) ◽  
pp. 364-376 ◽  
Author(s):  
Dongsun Cao ◽  
Zhigao Wang ◽  
Chun-Li Zhang ◽  
Jiyeon Oh ◽  
Weibing Xing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Transcriptional Activation ◽  
Histone Deacetylases ◽  
Serum Response Factor ◽  
Gene Activation ◽  
Muscle Gene Expression ◽  
P300 Binding ◽  
Muscle Genes ◽  
Muscle Gene

ABSTRACT Differentiation of smooth muscle cells is accompanied by the transcriptional activation of an array of muscle-specific genes controlled by serum response factor (SRF). Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. Here, we show that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of smooth muscle genes. The promyogenic activity of myocardin is enhanced by p300, a histone acetyltransferase that associates with the transcription activation domain of myocardin. Conversely, class II histone deacetylases interact with a domain of myocardin distinct from the p300-binding domain and suppress smooth muscle gene activation by myocardin. These findings point to myocardin as a nexus for positive and negative regulation of smooth muscle gene expression by changes in chromatin acetylation.

scholarly journals Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro.

1990 ◽  
Vol 87 (11) ◽  
pp. 4275-4279 ◽  
Author(s):  
H. Ito ◽  
S. C. Miller ◽  
M. E. Billingham ◽  
H. Akimoto ◽  
S. V. Torti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Muscle ◽  
Muscle Cells ◽  
Cardiac Muscle Cells ◽  
Muscle Gene Expression ◽  
Muscle Gene
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