Pathway Human Homo sapiens

Transcriptional regulation of pluripotent stem cells

R-HSA-452723 in Reactome release 97: under Developmental Biology, with 32 genes placed in it by the mapping files and 2 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id; neither of the other two lists holds it. Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-452723.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2014-03-12
Last updated: 2021-09-15
Events inside: 14, counted from the record

Pluripotent stem cells are undifferentiated cells posessing an abbreviated cell cycle (reviewed in Stein et al. 2012), a characteristic profile of gene expression (Rao et al. 2004, Kim et al. 2006, Player et al. 2006, Wang et al 2006 using mouse, International Stem Cell Initiative 2007, Assou et al. 2007, Assou et al. 2009, Ding et al. 2012 using mouse), and the ability to self-renew and generate all cell types of the body except extraembryonic lineages (Marti et al. 2013, reviewed in Romeo et al. 2012). They are a major cell type in the inner cell mass of the early embryo in vivo, and cells with the same properties, induced pluripotent stem cells, can be generated in vitro from differentiated adult cells by overexpression of a set of transcription factor genes (Takahashi and Yamanaka 2006, Takahashi et al. 2007, Yu et al. 2007, Jaenisch and Young 2008, Stein et al. 2012, reviewed in Dejosez and Zwaka 2012).

Pluripotency is maintained by a self-reinforcing loop of transcription factors (Boyer et al. 2005, Rao et al. 2006, Matoba et al. 2006, Player et al. 2006, Babaie et al. 2007, Sun et al. 2008, Assou et al. 2009, reviewed in Kashyap et al. 2009, reviewed in Dejosez and Zwaka 2012). In vivo, initiation of pluripotency may depend on maternal factors transmitted through the oocyte (Assou et al. 2009) and on DNA demethylation in the zygote (recently reviewed in Seisenberger et al. 2013) and hypoxia experienced by the blastocyst in the reproductive tract before implantation (Forristal et al. 2010, reviewed in Mohyeldin et al. 2010). In vitro, induced pluripotency may initiate with demethylation and activation of the promoters of POU5F1 (OCT4) and NANOG (Bhutani et al. 2010). Hypoxia also significantly enhances conversion to pluripotent stem cells (Yoshida et al. 2009). POU5F1 and NANOG, together with SOX2, encode central factors in pluripotency and activate their own transcription (Boyer et al 2005, Babaie et al. 2007, Yu et al. 2007, Takahashi et al. 2007). The autoactivation loop maintains expression of POU5F1, NANOG, and SOX2 at high levels in stem cells and, in turn, complexes containing various combinations of these factors (Remenyi et al. 2003, Lam et al. 2012) activate the expression of a group of genes whose products are associated with rapid cell proliferation and repress the expression of a group of genes whose products are associated with cell differentiation (Boyer et al. 2005, Matoba et al. 2006, Babaie et al. 2007, Chavez et al. 2009, Forristal et al. 2010, Guenther 2011).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 32 genes in this human pathway; showing 1 to 32, in pages of 100, sorted by symbol for reading. The order carries no ranking. 1 of the rows shown carries an id the identity file does not name, kept as the source wrote it.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneCDX2	AuthorityHGNC:1806	Mapping file idENSG00000165556 Ensembl file	EvidenceTAS
GeneCRIPTO	AuthorityHGNC:11701	Mapping file id6997 NCBI file	EvidenceTAS
GeneDKK1	AuthorityHGNC:2891	Mapping file idENSG00000107984 Ensembl file	EvidenceTAS
GeneDPPA4	AuthorityHGNC:19200	Mapping file id55211 NCBI file	EvidenceTAS
GeneEOMES	AuthorityHGNC:3372	Mapping file idENSG00000163508 Ensembl file	EvidenceTAS
GeneEPAS1	AuthorityHGNC:3374	Mapping file id2034 NCBI file	EvidenceTAS
GeneEPHA1	AuthorityHGNC:3385	Mapping file id2041 NCBI file	EvidenceTAS
GeneFGF2	AuthorityHGNC:3676	Mapping file id2247 NCBI file	EvidenceTAS
GeneFOXD3	AuthorityHGNC:3804	Mapping file id27022 NCBI file	EvidenceTAS
GeneFOXP1	AuthorityHGNC:3823	Mapping file id27086 NCBI file	EvidenceTAS
GeneGATA6	AuthorityHGNC:4174	Mapping file idENSG00000141448 Ensembl file	EvidenceTAS
GeneGSC	AuthorityHGNC:4612	Mapping file idENSG00000133937 Ensembl file	EvidenceTAS
GeneHHEX	AuthorityHGNC:4901	Mapping file idENSG00000152804 Ensembl file	EvidenceTAS
GeneHIF3A	AuthorityHGNC:15825	Mapping file id64344 NCBI file	EvidenceTAS
GeneKLF4	AuthorityHGNC:6348	Mapping file id9314 NCBI file	EvidenceTAS
GeneLIN28A	AuthorityHGNC:15986	Mapping file id79727 NCBI file	EvidenceTAS
GeneNANOG	AuthorityHGNC:20857	Mapping file id79923 NCBI file	EvidenceTAS
GeneNR5A1	AuthorityHGNC:7983	Mapping file id2516 NCBI file	EvidenceTAS
GeneNR6A1	AuthorityHGNC:7985	Mapping file id2649 NCBI file	EvidenceTAS
GenePBX1	AuthorityHGNC:8632	Mapping file id5087 NCBI file	EvidenceTAS
GenePOU5F1	AuthorityHGNC:9221	Mapping file id5460 NCBI file	EvidenceTAS
GenePRDM14	AuthorityHGNC:14001	Mapping file id63978 NCBI file	EvidenceTAS
GeneSALL1	AuthorityHGNC:10524	Mapping file id6299 NCBI file	EvidenceTAS
GeneSALL4	AuthorityHGNC:15924	Mapping file id57167 NCBI file	EvidenceTAS
GeneSMAD2	AuthorityHGNC:6768	Mapping file id4087 NCBI file	EvidenceTAS
GeneSMAD4	AuthorityHGNC:6770	Mapping file id4089 NCBI file	EvidenceTAS
GeneSOX2	AuthorityHGNC:11195	Mapping file id6657 NCBI file	EvidenceTAS
GeneSTAT3	AuthorityHGNC:11364	Mapping file id6774 NCBI file	EvidenceTAS
GeneTSC22D1	AuthorityHGNC:16826	Mapping file idENSG00000102804 Ensembl file	EvidenceTAS
GeneZIC3	AuthorityHGNC:12874	Mapping file id7547 NCBI file	EvidenceTAS
GeneZSCAN10	AuthorityHGNC:12997	Mapping file id84891 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file idNM_001244810 as written	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Developmental BiologyR-HSA-12667381,589 genes

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.