ZFIN ID: ZDB-PUB-161215-13
Distinct molecular signature of murine fetal liver and adult hematopoietic stem cells identifies novel regulators of hematopoietic stem cell function
Manesia, J.K., Franch, M., Tabas-Madrid, D., Nogales-Cadenas, R., Vanwelden, T., Van Den Bosch, E., Xu, Z., Pascual-Montano, A., Khurana, S., Verfaillie, C.
Date: 2017
Source: Stem cells and development   26(8): 573-584 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Adult Stem Cells/cytology
  • Adult Stem Cells/metabolism*
  • Animals
  • Cells, Cultured
  • Embryonic Stem Cells/cytology
  • Embryonic Stem Cells/metabolism*
  • Gene Expression Regulation, Developmental
  • Hematopoiesis/genetics*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Liver/cytology*
  • Liver/embryology
  • Mice
  • Mice, Inbred C57BL
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transcriptome*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 27958775 Full text @ Stem Cells Dev.
During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, while HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA-sequencing based gene expression analysis on FL HSCs from 14.5 day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed this data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1400 differentially expressed genes. More than 200 genes were shortlisted based on the GO annotation term "transcription". By morpholino based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function.