Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids.
Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids.
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DOI：
10.1016/j.stem.2021.03.022
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发表时间：
2021-06-03
期刊：
影响因子：
23.9
通讯作者：
Muthuswamy SK
中科院分区：
文献类型：
--
作者：
Huang L;Desai R;Conrad DN;Leite NC;Akshinthala D;Lim CM;Gonzalez R;Muthuswamy LB;Gartner Z;Muthuswamy SK
The exocrine pancreas, consisting of ducts and acini, is the site of origin of pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Our understanding of the genesis and progression of human pancreatic diseases, including PDAC, is limited because of challenges in maintaining human acinar and ductal cells in culture. Here we report induction of human pluripotent stem cells toward pancreatic ductal and acinar organoids that recapitulate properties of the neonatal exocrine pancreas. Expression of the PDAC-associated oncogene GNASR201C induces cystic growth more effectively in ductal than acinar organoids, whereas KRASG12D is more effective in modeling cancer in vivo when expressed in acinar compared with ductal organoids. KRASG12D, but not GNASR201C, induces acinar-to-ductal metaplasia-like changes in culture and in vivo. We develop a renewable source of ductal and acinar organoids for modeling exocrine development and diseases and demonstrate lineage tropism and plasticity for oncogene action in the human pancreas. Generation and long-term maintenance of human acinar organoids from stem cells GNASR201C induces cystic growth more effectively in ductal than in acinar organoids KRASG12D induces cancerous lesions more often from acinar versus ductal organoids KRASG12D in acinar organoids induces an acinar-to-ductal metaplasia-like phenotype Huang et al. describe conditions for generation of pancreatic ductal and acinar organoids from human stem cells. Expression of KRASG12D or GNASR201C induced cell-lineage-specific phenotypes and cell-state plasticity in culture and in vivo, identifying a renewable source of ductal and acinar organoids for modeling development and diseases of the exocrine pancreas.
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影响因子：
7.3
作者：
Amato, Eliana;dal Molin, Marco;Mafficini, Andrea;Yu, Jun;Malleo, Giuseppe;Rusev, Borislav;Fassan, Matteo;Antonello, Davide;Sadakari, Yoshihiko;Castelli, Paola;Zamboni, Giuseppe;Maitra, Anirban;Salvia, Roberto;Hruban, Ralph H.;Bassi, Claudio;Capelli, Paola;Lawlor, Rita T.;Goggins, Michael;Scarpa, Aldo
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Scarpa, Aldo
EMT亚型影响上皮可塑性和细胞迁移模式。
影响因子：
11.8
作者：
Aiello NM;Maddipati R;Norgard RJ;Balli D;Li J;Yuan S;Yamazoe T;Black T;Sahmoud A;Furth EE;Bar-Sagi D;Stanger BZ
通讯作者：
Stanger BZ
影响因子：
9.9
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Gillies TE;Pargett M;Silva JM;Teragawa CK;McCormick F;Albeck JG
通讯作者：
Albeck JG
影响因子：
29.4
作者：
Ideno N;Yamaguchi H;Ghosh B;Gupta S;Okumura T;Steffen DJ;Fisher CG;Wood LD;Singhi AD;Nakamura M;Gutkind JS;Maitra A
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影响因子：
82.9
作者：
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通讯作者：
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