SALL4 is a key transcription regulator in normal human hematopoiesis
Open accessAbstract
BACKGROUND: Stem cell factor SALL4 is a zinc finger transcription factor. It plays vital roles in the maintenance of embryonic stem cell properties, functions as an oncogene in leukemia, and has been recently proposed to use for cord blood expansion. The mechanism(s) by which SALL4 functions in normal human hematopoiesis, including identification of its target genes, still need to be explored. STUDY DESIGN AND METHODS: Chromatin immunoprecipitation followed by microarray hybridization (ChIP‐chip) was used for mapping SALL4 global gene targets in normal primary CD34+ cells. The results were then correlated with SALL4 functional studies in the CD34+ cells. RESULTS: More than 1000 potential SALL4 downstream target genes have been identified, and validation of binding by ChIP‐quantitative polymerase chain reaction was performed for 5% of potential targets. These include genes that are involving in hematopoietic differentiation and self‐renewal, such as HOXA9, RUNX1, CD34, and PTEN. Down regulation of SALL4 expression using small‐hairpin RNA in these cells led to decreased in vitro myeloid colony–forming abilities and impaired in vivo engraftment. Furthermore, HOXA9 was identified to be a major SALL4 target in normal human hematopoiesis and the loss of either SALL4 or HOXA9 expression in CD34+ cells shared a similar phenotype. CONCLUSION: Taken together, SALL4 is a key regulator in normal human hematopoiesis and the mechanism of its function is at least in part through the HOXA9. Future study will determine whether modulating the SALL4/HOXA9 pathway can be used in cellular therapy such as cord blood expansion and/or myeloid engraftment.
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Neither POU5F1 nor the 16 validated genes (except HN1) from Gao et al. (2013b) were significantly changed in RNA sequencing upon SALL4 knockdown in melanoma cells.
“neither POU5F1 nor the 16 validated genes (except for HN1) from Gao et al., (2013b) were significantly changed in our RNA sequencing upon SALL4 knockdown in melanoma cells”
From Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4 (2021) · cites this paper as Gao et al., (2013b)
In adult human tissue, SALL4 expression is thought to be restricted to testis and ovaries and hematopoietic stem/progenitor cells.
“SALL4 expression in adult human tissue is thought to be restricted to testis and ovaries64 and hematopoietic stem/progenitor cells (HSPCs)43.”
From Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4 (2021) · cites this paper as [43]
Other previously identified direct targets of SALL4 have not come up in our analyses.
“In addition, other previously identified direct targets of SALL443 have not come up in our analyses either”
From Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4 (2021) · cites this paper as [43]
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- Authors
- Gao, C., Kong, N. R., Li, A., Tatetu, H., Ueno, S., Yang, Y., He, J., Yang, J., Ma, Y., Kao, G. S., Tenen, D. G., & Chai, L.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Chai, Li
- Venue
- Transfusion
- Publisher
- Wiley
- Published
- 2012-08-31
- Volume
- 53
- Issue
- 5
- Pages
- 1037-1049
- ISSN
- 0041-1132 (ISSN-L)
- 1537-2995
- PMC
- PMC3653586
- OpenAlex
- W1507042016
- Cited by
- 58
- References
- 33
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 4 · 2013: 7
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Transfusion (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- National University of Singapore (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL092437, R01HL112719, P01HL095489)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK080665, DK080665, K08DK063220)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SALL4, hematopoiesis, transcriptional regulation, HOXA9, CD34+ hematopoietic progenitor cells, hematopoietic differentiation, myeloid colony formation, engraftment, zinc finger transcription factor
- MeSH terms
- Animals, Cell Differentiation, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Humans, Transcription Factors, Polymerase Chain Reaction, Hematopoietic Stem Cell Transplantation, Homeodomain Proteins, Antigens, CD34, Oligonucleotide Array Sequence Analysis, Chromatin Immunoprecipitation, Mice
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