Adult human pancreas-derived cells expressing stage-specific embryonic antigen 4 differentiate into Sox9-expressing and Ngn3-expressing pancreatic ducts in vivo.
Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. Here, we examined the characteristics and lineage-specific differentiation capacity of SSEA-4+cells.



Human adult partial pancreas tissues were obtained from different donors and cultured in vitro. SSEA-4+and CA19-9+cells were isolated from adult human pancreas exocrine cells using magnetic-activated cell sorting, and gene expression was validated by quantitative polymerase chain reaction. To confirm in-vivo differentiation, SSEA-4+and CA19-9+cells were transplanted into the dorsal subcutaneous region of mice. Finally, morphological features of differentiated areas were confirmed by immunostaining and morphometric analysis.



SSEA-4-expressing cells were detected in isolated pancreas exocrine cells from adult humans. These SSEA-4+cells exhibited coexpression of CA19-9, a marker of pancreatic duct cells, but not amylase expression, as shown by immunostaining and flow cytometry. SSEA-4+cells exhibited higher relative expression of Oct4, Nanog, Klf4, Sox2, and c-Myc mRNAs than CA19-9+cells. Pancreatic intralobular ducts (PIDs) were generated from SSEA-4+or CA19-9+cells in vivo at 5 weeks after transplantation. However, newly formed PIDs from CA19-9+cells were less abundant and showed an incomplete PID morphology. In contrast, newly formed PIDs from SSEA-4+cells were abundant in the transplanted area and showed a crowded morphology, typical of PIDs. Sox9 and Ngn3, key transcription factors associated with pancreatic development and regeneration, were expressed in PIDs from SSEA-4+cells.



SSEA-4-expressing cells in the adult human pancreas may have the potential for regeneration of the pancreas and may be used as a source of stem/progenitor cells for pancreatic cell lineage-specific differentiation.
Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.|Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
Song
S
Lee
Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.|Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
Chan Mi
CM
Lee
Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea. drksc@amc.seoul.kr.|Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea. drksc@amc.seoul.kr.
Song Cheol
0000-0003-4552-4169
SC
Kim
D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology; D010183:Pancreatic Ducts / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014182:Transplantation, Autologous / Q000379:methods
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D000090062:Kruppel-Like Factor 4; D009419:Nerve Tissue Proteins; D055758:SOX9 Transcription Factor; D055746:Stage-Specific Embryonic Antigens; D014157:Transcription Factors; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C498695:NEUROG3 protein, human; C527932:SOX9 protein, human; C066584:stage-specific embryonic antigen-4
Adult human pancreas; Adult stem cells; Embryonic-like stem cells; Pancreatic duct; Stage-specific embryonic antigen 4