Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation.
The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages. Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.
Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology & Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Palo Alto, California 94305, USA.
Kehkooi
K
Kee
Vanessa T
VT
Angeles
Martha
M
Flores
Ha Nam
HN
Nguyen
Renee A
RA
Reijo Pera
D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D000075364:Deleted in Azoospermia 1 Protein; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D006238:Haploidy; D006801:Humans; D008297:Male; D008540:Meiosis; D009928:Organ Specificity; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C481351:BOLL protein, human; D019485:Bone Morphogenetic Proteins; C095668:DAZ1 protein, human; C101358:DAZL protein, human; D000075364:Deleted in Azoospermia 1 Protein; D016601:RNA-Binding Proteins