Robust cellular reprogramming occurs spontaneously during liver regeneration

Cellular reprogramming-the ability to interconvert distinct cell types with defined factors-is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that medi...

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Vydané v:	Genes & development Ročník 27; číslo 7; s. 719
Hlavní autori:	Yanger, Kilangsungla, Zong, Yiwei, Maggs, Lara R, Shapira, Suzanne N, Maddipati, Ravi, Aiello, Nicole M, Thung, Swan N, Wells, Rebecca G, Greenbaum, Linda E, Stanger, Ben Z
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.04.2013
Predmet:	Animals Cell Lineage Epithelial Cells - cytology Epithelial Cells - metabolism Hepatocytes - cytology Hepatocytes - metabolism Liver Regeneration - physiology Mice Receptors, Notch - metabolism Signal Transduction Stem Cells - cytology
ISSN:	1549-5477, 1549-5477
On-line prístup:	Zistit podrobnosti o prístupe
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Abstract	Cellular reprogramming-the ability to interconvert distinct cell types with defined factors-is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions.
AbstractList	Cellular reprogramming-the ability to interconvert distinct cell types with defined factors-is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions.Cellular reprogramming-the ability to interconvert distinct cell types with defined factors-is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions. Cellular reprogramming-the ability to interconvert distinct cell types with defined factors-is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions.
Author	Aiello, Nicole M Thung, Swan N Greenbaum, Linda E Maggs, Lara R Stanger, Ben Z Shapira, Suzanne N Yanger, Kilangsungla Maddipati, Ravi Wells, Rebecca G Zong, Yiwei
Author_xml	– sequence: 1 givenname: Kilangsungla surname: Yanger fullname: Yanger, Kilangsungla organization: Department of Medicine, Gastroenterology Division – sequence: 2 givenname: Yiwei surname: Zong fullname: Zong, Yiwei – sequence: 3 givenname: Lara R surname: Maggs fullname: Maggs, Lara R – sequence: 4 givenname: Suzanne N surname: Shapira fullname: Shapira, Suzanne N – sequence: 5 givenname: Ravi surname: Maddipati fullname: Maddipati, Ravi – sequence: 6 givenname: Nicole M surname: Aiello fullname: Aiello, Nicole M – sequence: 7 givenname: Swan N surname: Thung fullname: Thung, Swan N – sequence: 8 givenname: Rebecca G surname: Wells fullname: Wells, Rebecca G – sequence: 9 givenname: Linda E surname: Greenbaum fullname: Greenbaum, Linda E – sequence: 10 givenname: Ben Z surname: Stanger fullname: Stanger, Ben Z
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23520387$$D View this record in MEDLINE/PubMed
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Snippet	Cellular reprogramming-the ability to interconvert distinct cell types with defined factors-is transforming the field of regenerative medicine. However, this...
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SubjectTerms	Animals Cell Lineage Epithelial Cells - cytology Epithelial Cells - metabolism Hepatocytes - cytology Hepatocytes - metabolism Liver Regeneration - physiology Mice Receptors, Notch - metabolism Signal Transduction Stem Cells - cytology
Title	Robust cellular reprogramming occurs spontaneously during liver regeneration
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