Generation of functional hepatocytes from mouse induced pluripotent stem cells.
Induced pluripotent stem cells are derived from somatic cells by forced expression of several transcriptional factors. Induced pluripotent stem cells resemble embryonic stem cells in many aspects, such as the expression of certain stem cell markers, chromatin methylation patterns, embryoid body formation and teratoma formation. Therefore, induced pluripotent stem cells provide a powerful tool for study of developmental biology and unlimited resources for transplantation therapy. Here we reported the successful induction of mouse induced pluripotent stem cells and a simple and efficient process for generation of functional hepatocytes from mouse induced pluripotent stem cells by sequential addition of inducing factors. These induced pluripotent stem cell-derived hepatocytes, just as mouse embryonic stem cell-derived hepatocytes, expressed hepatic lineage markers including CK7, CK8, CK18, CK19, alpha-fetoprotein, albumin, Cyp7a1, and exhibited functional hepatic characteristics, including glycogen storage, indocyanine green (ICG) uptake and release, low-density lipoprotein (LDL) uptake and urea secretion. Although we observed some variations in the efficiency of hepatic differentiation between induced pluripotent stem cells and common mouse embryonic stem cell lines, our results indicate that mouse induced pluripotent stem cells can efficiently differentiate into functional hepatocytes in vitro, which may be helpful for the study of liver development and regenerative medicine.
Li
Weiqiang
W
Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, Guangzhou 510080, P.R.China.
Wang
Ding
D
Qin
Jie
J
Liu
Chang
C
Zhang
Qi
Q
Zhang
Xiuming
X
Yu
Xinbing
X
Lahn
Bruce T
BT
Mao
Frank Fuxiang
FF
Xiang
Andy Peng
AP
D000418:Albumins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007208:Indocyanine Green / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014508:Urea / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D000418:Albumins; D015415:Biomarkers; D002087:Butyrates; D008077:Lipoproteins, LDL; D014157:Transcription Factors; D000509:alpha-Fetoproteins; D007633:Keratins; D014508:Urea; D006003:Glycogen; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse; D007208:Indocyanine Green; D004121:Dimethyl Sulfoxide