PMID- 33400835 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20211214 IS - 1549-4918 (Electronic) IS - 1066-5099 (Linking) VI - 39 IP - 4 DP - 2021 Apr TI - Robust parameter design of human induced pluripotent stem cell differentiation protocols defines lineage-specific induction of anterior-posterior gut tube endodermal cells. PG - 429-442 LID - 10.1002/stem.3326 [doi] AB - Tissues and cells derived from pluripotent stem cells (PSC) are likely to become widely used in disease modeling, drug screening, and regenerative medicine. For these applications, the in vitro PSC differentiation process must be elaborately investigated and controlled to reliably obtain the desired end products. However, because traditional experimental methods, such as one factor at a time or brute-force approaches, are impractical for detailed screening of complex PSC cultivation conditions, more strategic and effective screening based on statistical design of experiments (DOE) ought to be indispensable. Among various DOE approaches, we regard robust parameter design (RPD) as particularly suited for differentiation protocol optimization due to its suitability for multifactorial screening. We confirmed the adaptability of RPD for investigating human induced PSC lineage specification toward anterior-posterior gut tube endodermal cells and clarified both the contribution of each cell signaling pathway and the effect of cell signaling condition alteration on marker RNA expression levels, while increasing the efficiency of the screening in 243-fold (18 vs 4374) compared with that of a brute-force approach. Specific induction of anterior foregut, hepatic, pancreatic, or mid-hindgut cells was achieved using seven iPSC strains with the optimal culture protocols established on the basis of RPD analysis. RPD has the potential to enable efficient construction and optimization of PSC differentiation protocols, and its use is recommended from fundamental research to mass production of PSC-derived products. CI - (c)AlphaMed Press 2021. FAU - Yasui, Ryota AU - Yasui R AUID- ORCID: 0000-0002-5088-7696 AD - Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. AD - Fundamental Research Laboratory, Eiken Chemical Co., Ltd., Nogi, Tochigi, Japan. FAU - Sekine, Keisuke AU - Sekine K AUID- ORCID: 0000-0001-5133-0876 AD - Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. AD - Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. AD - Laboratory of Cancer Cell Systems, National Cancer Center Research Institute, Tokyo, Japan. FAU - Yamaguchi, Kiyoshi AU - Yamaguchi K AD - Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Furukawa, Yoichi AU - Furukawa Y AD - Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Taniguchi, Hideki AU - Taniguchi H AD - Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. AD - Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. AD - Advanced Medical Research Center, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210115 PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (AFP protein, human) RN - 0 (Biomarkers) RN - 0 (CDX2 Transcription Factor) RN - 0 (CDX2 protein, human) RN - 0 (Homeodomain Proteins) RN - 0 (Octamer Transcription Factor-3) RN - 0 (POU5F1 protein, human) RN - 0 (Trans-Activators) RN - 0 (alpha-Fetoproteins) RN - 0 (pancreatic and duodenal homeobox 1 protein) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 107-92-6 (Butyric Acid) RN - 5688UTC01R (Tretinoin) SB - IM MH - Biomarkers/metabolism MH - Butyric Acid/pharmacology MH - CDX2 Transcription Factor/genetics/metabolism MH - *Cell Culture Techniques MH - Cell Differentiation/drug effects MH - Cell Line MH - Cell Lineage/drug effects MH - Endoderm/*cytology/drug effects/metabolism MH - Factor Analysis, Statistical MH - Fibroblast Growth Factor 2/pharmacology MH - Gene Expression MH - Homeodomain Proteins/genetics/metabolism MH - Humans MH - Induced Pluripotent Stem Cells/*cytology/drug effects/metabolism MH - Intestines/*cytology/drug effects/metabolism MH - Liver/*cytology/drug effects/metabolism MH - Octamer Transcription Factor-3/genetics/metabolism MH - Pancreas/*cytology/drug effects/metabolism MH - *Research Design MH - Signal Transduction MH - Trans-Activators/genetics/metabolism MH - Tretinoin/pharmacology MH - alpha-Fetoproteins/genetics/metabolism OTO - NOTNLM OT - anterior-posterior patterning OT - cell differentiation OT - design of experiments (DOE) OT - endoderm OT - induced pluripotent stem cells OT - pluripotent stem cells EDAT- 2021/01/06 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/01/05 17:12 PHST- 2020/06/08 00:00 [received] PHST- 2020/12/07 00:00 [accepted] PHST- 2021/01/06 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/01/05 17:12 [entrez] AID - 10.1002/stem.3326 [doi] PST - ppublish SO - Stem Cells. 2021 Apr;39(4):429-442. doi: 10.1002/stem.3326. Epub 2021 Jan 15.