Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages
Open accessAbstract
Stem cells self-renew or differentiate under the governance of a stem-cell-specific transcriptional program, with each transcription factor orchestrating the activities of a particular set of genes. Here we demonstrate that a single transcription factor is able to regulate distinct core circuitries in two different blastocyst-derived stem cell lines, embryonic stem cells (ESCs) and extraembryonic endoderm (XEN) cells. The transcription factor Sall4 is required for early embryonic development and for ESC pluripotency. Sall4 is also expressed in XEN cells, and depletion of Sall4 disrupts self-renewal and induces differentiation. Genome-wide analysis reveals that Sall4 is regulating different gene sets in ESCs and XEN cells, and depletion of Sall4 targets in the respective cell types induces differentiation. With Oct4, Sox2, and Nanog, Sall4 forms a crucial interconnected autoregulatory network in ESCs. In XEN cells, Sall4 regulates the key XEN lineage-associated genes Gata4, Gata6, Sox7, and Sox17. Our findings demonstrate how Sall4 functions as an essential stemness factor for two different stem cell lines.
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Previous studies of Sall4 binding to the ESC genome used mouse microarrays (ChIP-Chip) with coverage biased towards genes and promoters, and therefore do not provide genome-wide coverage.
“Previous studies of Sall4 binding to the ESC genome used mouse microarrays (ChIP-Chip), the coverage of which is heavily biased towards genes and promoters, and therefore do not provide genome-wide coverage”
From Sall4 controls differentiation of pluripotent cells independently of the Nucleosome Remodelling and Deacetylation (NuRD) complex (2016) · cites this paper as Lim et al., 2008
Cites
Sakaki-Yumoto, M., Kobayashi, C., Sato, A., Fujimura, S., Matsumoto, Y., Takasato, M., Kodama, T., Aburatani, H., Asashima, M., Yoshida, N., et al. (2006) · Development · doi:10.1242/dev.02457 · Cited by 264 · see citing works
Murine inner cell mass-derived lineages depend on Sall4 function
Elling, U., Klasen, C., Eisenberger, T., Anlag, K., & Treier, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607884103 · Cited by 186 · see citing works
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Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds.
Hou, P., Li, Y., Zhang, X., Liu, C., Guan, J., Li, H., Zhao, T., Ye, J., Yang, W., Liu, K., et al. (2013) · Science · doi:10.1126/science.1239278 · Cited by 1,402 · see citing works
Lu, J., Jeong, H., Kong, N., Yang, Y., Carroll, J., Luo, H. R., Silberstein, L. E., YupoMa, & Chai, L. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005577 · Cited by 168 · see citing works
“SALL4 is also essential for maintenance of pluripotent and self-renewal properties of embryonic stem cells (ESCs) by interacting with other two key regulators in ESCs, NANOG and OCT4 [16–19].”
Roles of Sall4 in the generation of pluripotent stem cells from blastocysts and fibroblasts
Tsubooka, N., Ichisaka, T., Okita, K., Takahashi, K., Nakagawa, M., & Yamanaka, S. (2009) · Genes to Cells · doi:10.1111/j.1365-2443.2009.01301.x · Cited by 154 · see citing works
SALL4, the missing link between stem cells, development and cancer
Tatetsu, H., Kong, N. R., Chong, G., Amabile, G., Tenen, D. G., & Chai, L. (2016) · Gene · doi:10.1016/j.gene.2016.02.019 · Cited by 130 · see citing works
Yuri, S., Fujimura, S., Nimura, K., Takeda, N., Toyooka, Y., Fujimura, Y.-I., Aburatani, H., Ura, K., Koseki, H., Niwa, H., et al. (2009) · Stem Cells · doi:10.1002/stem.14 · Cited by 103 · see citing works
Miller, A., Ralser, M., Kloet, S. L., Loos, R., Nishinakamura, R., Bertone, P., Vermeulen, M., & Hendrich, B. (2016) · Development · doi:10.1242/dev.139113 · Cited by 78 · see citing works
“Previous studies of Sall4 binding to the ESC genome used mouse microarrays (ChIP-Chip), the coverage of which is heavily biased towards genes and promoters, and therefore do not provide genome-wide coverage (Lim et al., 2008; Rao et al., 2010; Tanimura et al., 2013; Yang et al., 2008; Yuri et al., 2009).”
BackgroundArtus, J., Douvaras, P., Piliszek, A., Isern, J., Baron, M. H., & Hadjantonakis, A.-K. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2011.10.015 · Cited by 83 · see citing works
Role of SALL4 in the progression and metastasis of colorectal cancer
Forghanifard, M. M., Moghbeli, M., Raeisossadati, R., Tavassoli, A., Mallak, A. J., Boroumand-Noughabi, S., & Abbaszadegan, M. R. (2013) · Journal of Biomedical Science · doi:10.1186/1423-0127-20-6 · Cited by 82 · see citing works
Lu, R., Yang, A., & Jin, Y. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202150 · Cited by 80 · see citing works
SALL4 is a key transcription regulator in normal human hematopoiesis
Gao, C., Kong, N. R., Li, A., Tatetu, H., Ueno, S., Yang, Y., He, J., Yang, J., Ma, Y., Kao, G. S., et al. (2013) · Transfusion · doi:10.1111/j.1537-2995.2012.03888.x · Cited by 58 · see citing works
Bode, D., Yu, L., Tate, P., Pardo, M., & Choudhary, J. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.053207 · Cited by 50 · see citing works
SALL4: An Intriguing Therapeutic Target in Cancer Treatment
Moein, S., Tenen, D. G., Amabile, G., & Chai, L. (2022) · Cells · doi:10.3390/cells11162601 · Cited by 35 · see citing works
Role of SALL4 in hematopoiesis
Yang, J., Liao, W., & Ma, Y. (2012) · Current Opinion in Hematology · doi:10.1097/moh.0b013e328353c684 · Cited by 17 · see citing works
- Authors
- Lim, C. Y., Tam, W.-L., Zhang, J., Ang, H. S., Jia, H., Lipovich, L., Ng, H.-H., Wei, C.-L., Sung, W. K., Robson, P., Yang, H., & Lim, B.
- Affiliations
- Genome Institute of Singapore (SG)
- Bioinformatics Institute (SG)
- National University of Singapore (SG)
- Harvard University (US)
- Corresponding author
- Tam, Wai-Leong
- Lim, Bing
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 3
- Issue
- 5
- Pages
- 543-554
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W1993333696
- Cited by
- 224
- References
- 2
- Citations by year
- 2025: 10 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 8 · 2018: 13 · 2017: 11 · 2016: 12 · 2015: 20 · 2014: 15 · 2013: 20 · 2012: 14
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1719 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- Genome Institute of Singapore
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI-54973, R01AI054973)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK047636, DK47636)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- SALL4, embryonic stem cells, extraembryonic endoderm, transcriptional circuitry, pluripotency, stemness, self-renewal, differentiation, Oct4, Nanog, SOX2, GATA4, GATA6, SOX7, SOX17
- MeSH terms
- Animals, Blastocyst, Cell Differentiation, Cell Line, Endoderm, High Mobility Group Proteins, Homeostasis, Transcription Factors, Transcriptional Activation, Gene Expression Regulation, Developmental, Cell Lineage, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA, Small Interfering, GATA Transcription Factors, Mice, Embryonic Stem Cells
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