Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages.
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.
Lim
Chin Yan
CY
Stem Cell and Developmental Biology, Genome Institute of Singapore, 138672 Singapore.
Tam
Wai-Leong
WL
Zhang
Jinqiu
J
Ang
Haw Siang
HS
Jia
Hui
H
Lipovich
Leonard
L
Ng
Huck-Hui
HH
Wei
Chia-Lin
CL
Sung
Wing Kin
WK
Robson
Paul
P
Yang
Henry
H
Lim
Bing
B
D000818:Animals; D001755:Blastocyst; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D050980:GATA Transcription Factors; D006609:High Mobility Group Proteins; D034741:RNA, Small Interfering; C472575:SALL4 protein, human; D014157:Transcription Factors