Species-specific developmental timing is maintained by pluripotent stem cells ex utero.
How species-specific developmental timing is controlled is largely unknown. By following human embryonic stem (ES) cell and mouse epiblast stem (EpiS) cell differentiation through detailed RNA-sequencing time courses, here we show that pluripotent stem cells closely retain in vivo species-specific developmental timing in vitro. In identical neural differentiation conditions in vitro, gene expression profiles are accelerated in mouse EpiS cells compared to human ES cells with relative rates of differentiation closely reflecting the rates of progression through the Carnegie stages in utero. Dynamic Time Warping analysis identified 3389 genes that were regulated more quickly in mouse EpiS cells and identified none that were regulated more quickly in human ES cells. Interestingly, we also find that human ES cells differentiated in teratomas maintain the same rate of differentiation observed in vitro in spite of being grown in a mouse host. These results suggest the existence of a cell autonomous, species-specific developmental clock that pluripotent stem cells maintain even out of context of an intact embryo.
Morgridge Institute for Research, Madison, WI 53715, USA.
Christopher
C
Barry
Morgridge Institute for Research, Madison, WI 53715, USA.
Matthew T
MT
Schmitz
Morgridge Institute for Research, Madison, WI 53715, USA.
Peng
P
Jiang
Center for Sustainable Nanotechnology, Department of Chemistry, University of Wisconsin-Madison, WI 53706, USA.
Michael P
MP
Schwartz
Morgridge Institute for Research, Madison, WI 53715, USA.
Bret M
BM
Duffin
Morgridge Institute for Research, Madison, WI 53715, USA.
Scott
S
Swanson
Department of Statistics, University of Wisconsin-Madison, WI 53706, USA.
Rhonda
R
Bacher
Morgridge Institute for Research, Madison, WI 53715, USA.
Jennifer M
JM
Bolin
Morgridge Institute for Research, Madison, WI 53715, USA.
Angela L
AL
Elwell
Morgridge Institute for Research, Madison, WI 53715, USA.
Brian E
BE
McIntosh
Morgridge Institute for Research, Madison, WI 53715, USA.
Ron
R
Stewart
Morgridge Institute for Research, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA. Electronic address: jthomson@morgridge.org.
James A
JA
Thomson
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016513:Mice, SCID; D009474:Neurons / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013045:Species Specificity; D013724:Teratoma / Q000473:pathology; D013997:Time Factors
Brain development; Developmental time; Differentiation; Embryonic stem cells