Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.

Journal article


Mylona, A., Andrieu-Soler, C., Thongjuea, S., Martella, A., Soler, E., Jorna, R., Hou, J., Kockx, C., van Ijcken, W., Lenhard, B. and Grosveld, F. 2013. Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis. Blood. 121 (15). https://doi.org/10.1182/blood-2012-11-467654
AuthorsMylona, A., Andrieu-Soler, C., Thongjuea, S., Martella, A., Soler, E., Jorna, R., Hou, J., Kockx, C., van Ijcken, W., Lenhard, B. and Grosveld, F.
Abstract

The first site exhibiting hematopoietic activity in mammalian development is the yolk-sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in blast colony-forming cells to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk-sac hematopoiesis and vascular development in Ldb1 -/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genomewide binding pattern of Ldb1 in hemangioblasts revealed a number of direct-target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signaling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.

Year2013
JournalBlood
Journal citation121 (15)
PublisherAmerican Society of Hematology
ISSN0006-4971
Digital Object Identifier (DOI)https://doi.org/10.1182/blood-2012-11-467654
Publication dates
Print11 Apr 2013
Publication process dates
Deposited15 Jan 2015
Accepted06 Feb 2013
Accepted author manuscript
Supplemental file
Output statusPublished
Permalink -

https://repository.canterbury.ac.uk/item/8730z/genome-wide-analysis-shows-that-ldb1-controls-essential-hematopoietic-genes-pathways-in-mouse-early-development-and-reveals-novel-players-in-hematopoiesis

Download files

Accepted author manuscript

Supplemental file
  • 29
    total views
  • 159
    total downloads
  • 1
    views this month
  • 4
    downloads this month

Export as

Related outputs

Utilising DOE to optimise hydrogel composition for tissue engineering
UPTON, A., Tirnoveanu, A., Thapa, G., Zimbitas, G., Mylona, A. and Webb, R. 2022. Utilising DOE to optimise hydrogel composition for tissue engineering.
Rheological properties of bioinks for printing optimisation
Upton, A., Thapa, G., Zimbitas, G., Mylona, A. and Webb, R. 2022. Rheological properties of bioinks for printing optimisation.
Proteomic analysis of the extracellular vesicles derived from human hip joints affected by osteoarthritis
Tirnoveanu, A., Ahmed, S., Webb, R., Howland, K., Hurt, A., Wilson, C. and Mylona, A. 2022. Proteomic analysis of the extracellular vesicles derived from human hip joints affected by osteoarthritis.
Enhanced bone marrow derived mesenchymal stem cell differentiation when isolated and expanded with human platelet rich plasma and differentiation media is supplemented with vitamin D
Thapa, G., Tirnoveanu, A., Mylona, A. and Webb, R. 2020. Enhanced bone marrow derived mesenchymal stem cell differentiation when isolated and expanded with human platelet rich plasma and differentiation media is supplemented with vitamin D. eCM Periodicals & Conferences.
Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia
Zambetti, N., Ping, Z., Chen, S., Kenswill, K., Mylona, A., Sanders, M., Hoogenboezem, R., Bindels, E., Adisty, N., Van Strien, P., van der Leije, C., Westers, T., Cremers, E., Milanese, C., Mastroberardino, P., van Leeuwen, J., van der Eerden, B., Touw, I., Kuijpers, T., Kanaar, R., van der Loosdrecht, A., Vogl, T. and Raaijmakers, M. 2016. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell. 19 (5), pp. 613-627. https://doi.org/10.1016/j.stem.2016.08.021
The Isl1/Ldb1 complex orchestrates heart-specific chromatin organization and transcriptional regulation
Caputo, L., Witzel, H., Kolovos, P., Cheedipudi, S., Looso, M., Mylona, A., van Ijcken, W., Evans, S., Braun, T., Soler, E., Grosveld, F. and Dobreva, G. 2015. The Isl1/Ldb1 complex orchestrates heart-specific chromatin organization and transcriptional regulation. Cell Stem Cell. 17 (3), pp. 287-299. https://doi.org/10.1016/j.stem.2015.08.007
Massive parallel RNA sequencing of highly purified mesenchymal elements in low-risk MDS reveals tissue-context dependent activation of inflammatory programs
Chen, S., Zambetti, N., Bindels, E., Kenswill, K., Mylona, A., Adisty, N., Hoogenboezem, R., Sanders, M., Cremers, E., Jansen, J., van de Loosdrecht, A. and Raaijmakers, M. 2016. Massive parallel RNA sequencing of highly purified mesenchymal elements in low-risk MDS reveals tissue-context dependent activation of inflammatory programs. Leukemia. https://doi.org/10.1038/leu.2016.91
Genomic structure and cloning of two transcript isoforms of human Sp8.
Mylona, A., Gough, J. and Edgar, A. 2004. Genomic structure and cloning of two transcript isoforms of human Sp8. BMC Genomics. 5 (86). https://doi.org/10.1186/1471-2164-5-86