SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate

Naoko Irie, Leehee Weinberger, Walfred W.C. Tang,Toshihiro Kobayashi, Sergey Viukov, Yair S. Manor, Sabine Dietmann, Jacob H. Hanna and M. Azim Surani, 15.01.2015

Abstract

Specification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information.

IRIE, Naoko, et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell, 2015, 160. Jg., Nr. 1-2, S. 253-268.

Publication: https://doi.org/10.1016/j.cell.2014.12.013
Repository: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60138

Disclaimer

The publication SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate by Naoko Irie, Leehee Weinberger, Walfred W.C. Tang,Toshihiro Kobayashi, Sergey Viukov, Yair S. Manor, Sabine Dietmann, Jacob H. Hanna and M. Azim Surani is published under an open access license: https://creativecommons.org/licenses/by/3.0/. Permits to share, copy and redistribute the material in any medium or format and to adapt, remix, transform, and build upon the material for any purpose, even commercially.

Curation by the MFGA team
Relevant data sets presented in the publication have been identified. If possible, annotations (title, general information, conditions, processed tissue types and processed cell types) have been added based on information from the publication. Data tables and images that provide a good overview on the publication's findings on the data set have been extracted from the publication and/or supplement. If not stated otherwise, images are depicted with title and description exactly as in the publication. Tables have been adjusted to the MFGA table format. Conducted adjustments are explained in the detailed view of the tables. However, titles and descriptions have been adopted from the publication.

Data set 1: RNA-Seq results for human PGCLCs, PGCs, and TCam-2 Seminoma cells

Transcriptome: Single-cell RNA-Sequencing

Species

Species
Human

Tissue Types

BRENDA tissue ontology	Maturity	Description	Species	Replicates
BTO_0000379: embryo			Human
BTO_0000279: testicular cancer cell	Adult	Tcam-2 cells; Human testicular seminona cell line	Human	2.0

Cell Types

Cell ontology	Maturity	Description	Species	Replicates
CL_0002322: embryonic stem cell	Embryonic	Human 4i hESC (WIS2: 46XY; WIBR3: 46XX; LIS1, 46XY)	Human	4
CL_0002322: embryonic stem cell	Embryonic	human Pre-induced hESC	Human	2
	Primordial	Human primordial germ cell like cells (hPGCLCs)	Human	2
CL_0000670: primordial germ cell	Primordial	Human primordial germ cells (hPGCs)	Human	2
CL_0002371: somatic cell	Embryonic	Gonadal Somatic Cells (from developmental week 7 genital ridge)	Human	2
CL_0002322: embryonic stem cell	Embryonic	Human embryonic stem cell line; Conventional hESCs	Human	2

Images

Figure 2D

hPGCLC Shares Transcriptional Profile with Human Embryonic PGCs and TCam-2 Seminoma; (D) Venn diagram illustrates common and differentially expressed genes. Significantly upregulated genes in hPGCLC, gonadal hPGC, and TCam-2 (with log2 (fold change) > 3 and adjusted p value < 0.05 versus gonadal Soma, respectively) were compared. Representative genes that were exclusive to each category are indicated. Text boxes indicate gene ontology biological processes (BP) terms that were significantly enriched as indicated by p values. Asterisk denotes custom categories absent from BP annotation.

Source: IRIE, Naoko, et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell, 2015, 160. Jg., Nr. 1-2, S. 253-268.

Licensed under: https://creativecommons.org/licenses/by/3.0/

Figure 2C

hPGCLC Shares Transcriptional Profile with Human Embryonic PGCs and TCam-2 Seminoma; (C) Heat map of gene expression of key PGC-associated genes (early and late) and of pluripotency, mesoderm, endoderm, and gonadal somatic (Soma) markers.