Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells.
Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of germ cell-specific gene expression and initiation of embryonic-like programs. Furthermore, SSCs in vitro maintain the epigenomic characteristics of germ cells in vivo. Our observations suggest that SSCs encode innate plasticity through the epigenome and that both conversion of promoter chromatin states and activation of cell type-specific enhancers are prominent features of reprogramming.
Department of Medicine, Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA.|Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065, USA.
Ying
Y
Liu
Biological Sciences Department, New York City College of Technology, City University of New York, Brooklyn, New York 11201, USA.|Arthritis and Tissue Degeneration Program and the David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, New York 10021, USA.
Eugenia G
0000-0001-5773-5241
EG
Giannopoulou
Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
Duancheng
D
Wen
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
Ilaria
I
Falciatori
HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York 10065, USA.|Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.
Olivier
O
Elemento
Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065, USA.
C David
CD
Allis
Department of Medicine, Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA.
Shahin
S
Rafii
Department of Surgery, Weill Cornell Medical College, New York, New York 10065, USA.
Marco
M
Seandel
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D000066670:Cell Plasticity / Q000235:genetics*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism*; D057890:Epigenomics / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*
D006657:Histones; D008239:Lysine