Alternative titles; symbols
HGNC Approved Gene Symbol: TCF15
Cytogenetic location: 20p13 Genomic coordinates (GRCh38): 20:604,257-610,309 (from NCBI)
Basic helix-loop-helix (bHLH) factors play important roles in regulating development and differentiation in an invertebrate species. Quertermous et al. (1994) cloned and characterized a novel bHLH gene, bHLH-EC2, that is expressed in early mesoderm and in developing somites in the mouse embryo. Because of its homology to other bHLH proteins and its pattern of embryonic expression, it was postulated that it functions as an early transcriptional regulator, involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm. In keeping with established guidelines for gene terminology, this gene was designated TCF15. TCF refers to 'transcription factor' and is a designation provided by the HGM Nomenclature Group (Quertermous (1996)).
Blanar et al. (1995) cloned a member of the bHLH family of transcription factors, Meso1, in the mouse. It appeared that Meso1 is the mouse homolog of human TCF15.
Hidai et al. (1995) found that the mouse bHLH-EC2 gene consisted of 2 exons separated by a 5-kb intron, an organization pattern similar to that of the mouse 'twist' gene (601622). The transcription initiation site was identified by RNase protection assay and primer extension analysis. Linked promoter-reporter gene transfection experiments in cultured cells indicated that while the identified upstream sequence can function to promote transcription, it does not function in a cell-specific fashion.
Hidai et al. (1995) assigned the human TCF15 gene to 20p13 by fluorescence in situ hybridization.
The notion that mouse Meso1 is the mouse homolog of human TCF15 was supported by the fact that Blanar et al. (1995) mapped the Meso1 gene to the distal region of mouse chromosome 2 between Pax1 (167411) and Hck (142370), which in the human are located at 20p11.2 and 20q11-q12, respectively.
Rodriguez-Fraticelli et al. (2020) implemented expressible lentiviral barcoding, which enabled simultaneous analysis of lineages and transcriptomes from single adult hematopoietic stem cells and their clonal trajectories during long-term bone marrow reconstitution. Analysis of differential gene expression between clones with distinct behavior revealed an intrinsic molecular signature that characterizes functional long-term repopulating hematopoietic stem cells. Probing this signature through in vivo CRISPR screening, Rodriguez-Fraticelli et al. (2020) found the transcription factor TCF15 to be required and sufficient to drive hematopoietic stem cell quiescence and long-term self-renewal. In situ, TCF15 expression labels the most primitive subset of true multipotent hematopoietic stem cells.
In the vertebrate embryo, segmental organization becomes apparent when somites form in a rostrocaudal progression from the paraxial mesoderm adjacent to the neural tube. Newly formed somites appear as paired epithelial spheres that become patterned to form vertebrae, ribs, skeletal muscle, and dermis. To determine the function of Meso1, or paraxis, during development, Burgess et al. (1996) disrupted the mouse paraxis gene. In mice homozygous for a paraxis null mutation, cells from the paraxial mesoderm were unable to form epithelia, and so somite formation was disrupted. In the absence of normal somites, the axial skeleton and skeletal muscle formed but were improperly patterned. However, formation of epithelial somites was not required for segmentation of the embryo or for the establishment of somitic cell lineages. Burgess et al. (1996) concluded that paraxis regulates somite morphogenesis, and that the function of somites is to pattern the axial skeleton and skeletal muscles.
Blanar, M. A., Crossley, P. H., Peters, K. G., Steingrimsson, E., Copeland, N. G., Jenkins, N. A., Martin, G. R., Rutter, W. J. Meso1, a basic helix-loop-helix protein involved in mammalian presomitic mesoderm development. Proc. Nat. Acad. Sci. 92: 5870-5874, 1995. [PubMed: 7597044] [Full Text: https://doi.org/10.1073/pnas.92.13.5870]
Burgess, R., Rawls, A., Brown, D., Bradley, A., Olson, E. N. Requirement of the paraxis gene for somite formation and musculoskeletal patterning. Nature 384: 570-573, 1996. [PubMed: 8955271] [Full Text: https://doi.org/10.1038/384570a0]
Hidai, H., Quertermous, E. E., Espinosa, R., III, Le Beau, M. M., Quertermous, T. Genomic organization and chromosomal localization of the gene TCF15 encoding the early mesodermal basic helix-loop-helix factor bHLH-EC2. Genomics 30: 598-601, 1995. [PubMed: 8825648] [Full Text: https://doi.org/10.1006/geno.1995.1282]
Quertermous, E. E., Hidai, H., Blanar, M. A., Quertermous, T. Cloning and characterization of a basic helix-loop-helix protein expressed in early mesoderm and the developing somites. Proc. Nat. Acad. Sci. 91: 7066-7070, 1994. [PubMed: 8041747] [Full Text: https://doi.org/10.1073/pnas.91.15.7066]
Quertermous, T. Personal Communication. Nashville, Tenn. 1/22/1996.
Rodriguez-Fraticelli, A. E., Weinreb, C., Wang, S.-W., Migueles, R. P., Jankovic, M., Usart, M., Klein, A. M., Lowell, S., Camargo, F. D. Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis. Nature 583: 585-589, 2020. [PubMed: 32669716] [Full Text: https://doi.org/10.1038/s41586-020-2503-6]