Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development
The stem/progenitor cells of the developing intestine are biologically distinct from their adult counterparts. Here, we examine the microenvironmental cues that regulate the embryonic stem/progenitor population, focusing on the role of Notch pathway factor delta-like protein-1 (DLK1). mRNA-seq analy...
Gespeichert in:
| Veröffentlicht in: | American journal of physiology: Gastrointestinal and liver physiology 2021-04, Vol.320 (4), p.G506-G520 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | G520 |
|---|---|
| container_issue | 4 |
| container_start_page | G506 |
| container_title | American journal of physiology: Gastrointestinal and liver physiology |
| container_volume | 320 |
| creator | Ichinose, Mari Suzuki, Nobumi Wang, Tongtong Wright, Josephine A Lannagan, Tamsin R M Vrbanac, Laura Kobayashi, Hiroki Gieniec, Krystyna A Ng, Jia Q Hayakawa, Yoku García-Gallastegui, Patricia Monsalve, Eva M Bauer, Steven R Laborda, Jorge García-Ramírez, J J Ibarretxe, Gaskon Worthley, Daniel L Woods, Susan L |
| description | The stem/progenitor cells of the developing intestine are biologically distinct from their adult counterparts. Here, we examine the microenvironmental cues that regulate the embryonic stem/progenitor population, focusing on the role of Notch pathway factor delta-like protein-1 (DLK1). mRNA-seq analyses of intestinal mesenchymal cells (IMCs) collected from embryonic day 14.5 (E14.5) or adult IMCs and a novel coculture system with E14.5 intestinal epithelial organoids were used. Following addition of recombinant DLK1 (rDLK) or
siRNA (
), epithelial characteristics were compared using imaging, replating efficiency assays, qPCR, and immunocytochemistry. The intestinal phenotypes of littermate
and
mice were compared using immunohistochemistry. Using transcriptomic analyses, we identified morphogens derived from the embryonic mesenchyme that potentially regulate the developing epithelial cells, to focus on Notch family candidate DLK1. Immunohistochemistry indicated that DLK1 was expressed exclusively in the intestinal stroma at E14.5 at the top of emerging villi, decreased after birth, and shifted to the intestinal epithelium in adulthood. In coculture experiments, addition of rDLK1 to adult IMCs inhibited organoid differentiation, whereas
knockdown in embryonic IMCs increased epithelial differentiation to secretory lineage cells.
mice had restricted Ki67
cells in the villi base and increased secretory lineage cells compared with
embryos. Mesenchyme-derived DLK1 plays an important role in the promotion of epithelial stem/precursor expansion and prevention of differentiation to secretory lineages in the developing intestine.
Using a novel coculture system, transcriptomics, and transgenic mice, we investigated differential molecular signaling between the intestinal epithelium and mesenchyme during development and in the adult. We show that the Notch pathway factor delta-like protein-1 (DLK1) is stromally produced during development and uncover a new role for DLK1 in the regulation of intestinal epithelial stem/precursor expansion and differentiation to secretory lineages. |
| doi_str_mv | 10.1152/ajpgi.00445.2020 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2479421259</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2518415522</sourcerecordid><originalsourceid>FETCH-LOGICAL-c393t-d6411c2c1b89c987174341f5d91e852b032bfbd45c63939fa05aa884b65cfd033</originalsourceid><addsrcrecordid>eNpdkbtPwzAQxi0EglLYmVAkFpYUnx9NPCLeohIDMFtObLeu8iJOkPjvubbAwOTTfb_v5LuPkDOgMwDJrsy6W4YZpULIGaOM7pEJtlkKUmT7ZEJB8RRymR2R4xjXlFLJAA7JEecio5CzCeleh76tTZXcLp4h6bBuBxc3RRW8680Q2iYxjU1CswpFGGJig0fBNUPYia1PhpVDHX1DaHCU6wJ2qjDWiR370CwT6z5d1XY1uk7IgTdVdKc_75S839-93Tymi5eHp5vrRVpyxYfUzgVAyUooclWqPINMcAFeWgUul6ygnBW-sEKWc-SVN1Qak-eimMvSW8r5lFzu5uIqHyN-Tdchlq6qTOPaMWomMiUYMKkQvfiHrtuxx02QkpALkHhTpOiOKvs2xt553fWhNv2XBqo3aehtGnqbht6kgZbzn8FjUTv7Z_g9P_8G2AOHYQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2518415522</pqid></control><display><type>article</type><title>Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development</title><source>MEDLINE</source><source>American Physiological Society</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Ichinose, Mari ; Suzuki, Nobumi ; Wang, Tongtong ; Wright, Josephine A ; Lannagan, Tamsin R M ; Vrbanac, Laura ; Kobayashi, Hiroki ; Gieniec, Krystyna A ; Ng, Jia Q ; Hayakawa, Yoku ; García-Gallastegui, Patricia ; Monsalve, Eva M ; Bauer, Steven R ; Laborda, Jorge ; García-Ramírez, J J ; Ibarretxe, Gaskon ; Worthley, Daniel L ; Woods, Susan L</creator><creatorcontrib>Ichinose, Mari ; Suzuki, Nobumi ; Wang, Tongtong ; Wright, Josephine A ; Lannagan, Tamsin R M ; Vrbanac, Laura ; Kobayashi, Hiroki ; Gieniec, Krystyna A ; Ng, Jia Q ; Hayakawa, Yoku ; García-Gallastegui, Patricia ; Monsalve, Eva M ; Bauer, Steven R ; Laborda, Jorge ; García-Ramírez, J J ; Ibarretxe, Gaskon ; Worthley, Daniel L ; Woods, Susan L</creatorcontrib><description>The stem/progenitor cells of the developing intestine are biologically distinct from their adult counterparts. Here, we examine the microenvironmental cues that regulate the embryonic stem/progenitor population, focusing on the role of Notch pathway factor delta-like protein-1 (DLK1). mRNA-seq analyses of intestinal mesenchymal cells (IMCs) collected from embryonic day 14.5 (E14.5) or adult IMCs and a novel coculture system with E14.5 intestinal epithelial organoids were used. Following addition of recombinant DLK1 (rDLK) or
siRNA (
), epithelial characteristics were compared using imaging, replating efficiency assays, qPCR, and immunocytochemistry. The intestinal phenotypes of littermate
and
mice were compared using immunohistochemistry. Using transcriptomic analyses, we identified morphogens derived from the embryonic mesenchyme that potentially regulate the developing epithelial cells, to focus on Notch family candidate DLK1. Immunohistochemistry indicated that DLK1 was expressed exclusively in the intestinal stroma at E14.5 at the top of emerging villi, decreased after birth, and shifted to the intestinal epithelium in adulthood. In coculture experiments, addition of rDLK1 to adult IMCs inhibited organoid differentiation, whereas
knockdown in embryonic IMCs increased epithelial differentiation to secretory lineage cells.
mice had restricted Ki67
cells in the villi base and increased secretory lineage cells compared with
embryos. Mesenchyme-derived DLK1 plays an important role in the promotion of epithelial stem/precursor expansion and prevention of differentiation to secretory lineages in the developing intestine.
Using a novel coculture system, transcriptomics, and transgenic mice, we investigated differential molecular signaling between the intestinal epithelium and mesenchyme during development and in the adult. We show that the Notch pathway factor delta-like protein-1 (DLK1) is stromally produced during development and uncover a new role for DLK1 in the regulation of intestinal epithelial stem/precursor expansion and differentiation to secretory lineages.</description><identifier>ISSN: 0193-1857</identifier><identifier>EISSN: 1522-1547</identifier><identifier>DOI: 10.1152/ajpgi.00445.2020</identifier><identifier>PMID: 33470182</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Animals ; Calcium-Binding Proteins - deficiency ; Calcium-Binding Proteins - genetics ; Calcium-Binding Proteins - metabolism ; Cell Communication ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Embryo cells ; Embryonic Stem Cells - enzymology ; Epithelial cells ; Epithelial Cells - enzymology ; Epithelium ; Gene Expression Regulation, Developmental ; Immunocytochemistry ; Immunohistochemistry ; Intestinal Mucosa - embryology ; Intestinal Mucosa - enzymology ; Intestine ; Mesenchyme ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Organoids ; Phenotypes ; Preadipocyte factor 1 ; Progenitor cells ; Secretory Pathway ; Signal Transduction ; siRNA ; Stem Cell Niche ; Stem cells ; Stroma ; Stromal Cells - enzymology ; Transcriptome</subject><ispartof>American journal of physiology: Gastrointestinal and liver physiology, 2021-04, Vol.320 (4), p.G506-G520</ispartof><rights>Copyright American Physiological Society Apr 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-d6411c2c1b89c987174341f5d91e852b032bfbd45c63939fa05aa884b65cfd033</citedby><cites>FETCH-LOGICAL-c393t-d6411c2c1b89c987174341f5d91e852b032bfbd45c63939fa05aa884b65cfd033</cites><orcidid>0000-0002-3988-2499 ; 0000-0002-8955-2017</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33470182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ichinose, Mari</creatorcontrib><creatorcontrib>Suzuki, Nobumi</creatorcontrib><creatorcontrib>Wang, Tongtong</creatorcontrib><creatorcontrib>Wright, Josephine A</creatorcontrib><creatorcontrib>Lannagan, Tamsin R M</creatorcontrib><creatorcontrib>Vrbanac, Laura</creatorcontrib><creatorcontrib>Kobayashi, Hiroki</creatorcontrib><creatorcontrib>Gieniec, Krystyna A</creatorcontrib><creatorcontrib>Ng, Jia Q</creatorcontrib><creatorcontrib>Hayakawa, Yoku</creatorcontrib><creatorcontrib>García-Gallastegui, Patricia</creatorcontrib><creatorcontrib>Monsalve, Eva M</creatorcontrib><creatorcontrib>Bauer, Steven R</creatorcontrib><creatorcontrib>Laborda, Jorge</creatorcontrib><creatorcontrib>García-Ramírez, J J</creatorcontrib><creatorcontrib>Ibarretxe, Gaskon</creatorcontrib><creatorcontrib>Worthley, Daniel L</creatorcontrib><creatorcontrib>Woods, Susan L</creatorcontrib><title>Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development</title><title>American journal of physiology: Gastrointestinal and liver physiology</title><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><description>The stem/progenitor cells of the developing intestine are biologically distinct from their adult counterparts. Here, we examine the microenvironmental cues that regulate the embryonic stem/progenitor population, focusing on the role of Notch pathway factor delta-like protein-1 (DLK1). mRNA-seq analyses of intestinal mesenchymal cells (IMCs) collected from embryonic day 14.5 (E14.5) or adult IMCs and a novel coculture system with E14.5 intestinal epithelial organoids were used. Following addition of recombinant DLK1 (rDLK) or
siRNA (
), epithelial characteristics were compared using imaging, replating efficiency assays, qPCR, and immunocytochemistry. The intestinal phenotypes of littermate
and
mice were compared using immunohistochemistry. Using transcriptomic analyses, we identified morphogens derived from the embryonic mesenchyme that potentially regulate the developing epithelial cells, to focus on Notch family candidate DLK1. Immunohistochemistry indicated that DLK1 was expressed exclusively in the intestinal stroma at E14.5 at the top of emerging villi, decreased after birth, and shifted to the intestinal epithelium in adulthood. In coculture experiments, addition of rDLK1 to adult IMCs inhibited organoid differentiation, whereas
knockdown in embryonic IMCs increased epithelial differentiation to secretory lineage cells.
mice had restricted Ki67
cells in the villi base and increased secretory lineage cells compared with
embryos. Mesenchyme-derived DLK1 plays an important role in the promotion of epithelial stem/precursor expansion and prevention of differentiation to secretory lineages in the developing intestine.
Using a novel coculture system, transcriptomics, and transgenic mice, we investigated differential molecular signaling between the intestinal epithelium and mesenchyme during development and in the adult. We show that the Notch pathway factor delta-like protein-1 (DLK1) is stromally produced during development and uncover a new role for DLK1 in the regulation of intestinal epithelial stem/precursor expansion and differentiation to secretory lineages.</description><subject>Animals</subject><subject>Calcium-Binding Proteins - deficiency</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Cell Communication</subject><subject>Cell Differentiation</subject><subject>Cell Lineage</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Embryo cells</subject><subject>Embryonic Stem Cells - enzymology</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - enzymology</subject><subject>Epithelium</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Immunocytochemistry</subject><subject>Immunohistochemistry</subject><subject>Intestinal Mucosa - embryology</subject><subject>Intestinal Mucosa - enzymology</subject><subject>Intestine</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, 129 Strain</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Organoids</subject><subject>Phenotypes</subject><subject>Preadipocyte factor 1</subject><subject>Progenitor cells</subject><subject>Secretory Pathway</subject><subject>Signal Transduction</subject><subject>siRNA</subject><subject>Stem Cell Niche</subject><subject>Stem cells</subject><subject>Stroma</subject><subject>Stromal Cells - enzymology</subject><subject>Transcriptome</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkbtPwzAQxi0EglLYmVAkFpYUnx9NPCLeohIDMFtObLeu8iJOkPjvubbAwOTTfb_v5LuPkDOgMwDJrsy6W4YZpULIGaOM7pEJtlkKUmT7ZEJB8RRymR2R4xjXlFLJAA7JEecio5CzCeleh76tTZXcLp4h6bBuBxc3RRW8680Q2iYxjU1CswpFGGJig0fBNUPYia1PhpVDHX1DaHCU6wJ2qjDWiR370CwT6z5d1XY1uk7IgTdVdKc_75S839-93Tymi5eHp5vrRVpyxYfUzgVAyUooclWqPINMcAFeWgUul6ygnBW-sEKWc-SVN1Qak-eimMvSW8r5lFzu5uIqHyN-Tdchlq6qTOPaMWomMiUYMKkQvfiHrtuxx02QkpALkHhTpOiOKvs2xt553fWhNv2XBqo3aehtGnqbht6kgZbzn8FjUTv7Z_g9P_8G2AOHYQ</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Ichinose, Mari</creator><creator>Suzuki, Nobumi</creator><creator>Wang, Tongtong</creator><creator>Wright, Josephine A</creator><creator>Lannagan, Tamsin R M</creator><creator>Vrbanac, Laura</creator><creator>Kobayashi, Hiroki</creator><creator>Gieniec, Krystyna A</creator><creator>Ng, Jia Q</creator><creator>Hayakawa, Yoku</creator><creator>García-Gallastegui, Patricia</creator><creator>Monsalve, Eva M</creator><creator>Bauer, Steven R</creator><creator>Laborda, Jorge</creator><creator>García-Ramírez, J J</creator><creator>Ibarretxe, Gaskon</creator><creator>Worthley, Daniel L</creator><creator>Woods, Susan L</creator><general>American Physiological Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3988-2499</orcidid><orcidid>https://orcid.org/0000-0002-8955-2017</orcidid></search><sort><creationdate>20210401</creationdate><title>Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development</title><author>Ichinose, Mari ; Suzuki, Nobumi ; Wang, Tongtong ; Wright, Josephine A ; Lannagan, Tamsin R M ; Vrbanac, Laura ; Kobayashi, Hiroki ; Gieniec, Krystyna A ; Ng, Jia Q ; Hayakawa, Yoku ; García-Gallastegui, Patricia ; Monsalve, Eva M ; Bauer, Steven R ; Laborda, Jorge ; García-Ramírez, J J ; Ibarretxe, Gaskon ; Worthley, Daniel L ; Woods, Susan L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-d6411c2c1b89c987174341f5d91e852b032bfbd45c63939fa05aa884b65cfd033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Calcium-Binding Proteins - deficiency</topic><topic>Calcium-Binding Proteins - genetics</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Cell Communication</topic><topic>Cell Differentiation</topic><topic>Cell Lineage</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Embryo cells</topic><topic>Embryonic Stem Cells - enzymology</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - enzymology</topic><topic>Epithelium</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Immunocytochemistry</topic><topic>Immunohistochemistry</topic><topic>Intestinal Mucosa - embryology</topic><topic>Intestinal Mucosa - enzymology</topic><topic>Intestine</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, 129 Strain</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Organoids</topic><topic>Phenotypes</topic><topic>Preadipocyte factor 1</topic><topic>Progenitor cells</topic><topic>Secretory Pathway</topic><topic>Signal Transduction</topic><topic>siRNA</topic><topic>Stem Cell Niche</topic><topic>Stem cells</topic><topic>Stroma</topic><topic>Stromal Cells - enzymology</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ichinose, Mari</creatorcontrib><creatorcontrib>Suzuki, Nobumi</creatorcontrib><creatorcontrib>Wang, Tongtong</creatorcontrib><creatorcontrib>Wright, Josephine A</creatorcontrib><creatorcontrib>Lannagan, Tamsin R M</creatorcontrib><creatorcontrib>Vrbanac, Laura</creatorcontrib><creatorcontrib>Kobayashi, Hiroki</creatorcontrib><creatorcontrib>Gieniec, Krystyna A</creatorcontrib><creatorcontrib>Ng, Jia Q</creatorcontrib><creatorcontrib>Hayakawa, Yoku</creatorcontrib><creatorcontrib>García-Gallastegui, Patricia</creatorcontrib><creatorcontrib>Monsalve, Eva M</creatorcontrib><creatorcontrib>Bauer, Steven R</creatorcontrib><creatorcontrib>Laborda, Jorge</creatorcontrib><creatorcontrib>García-Ramírez, J J</creatorcontrib><creatorcontrib>Ibarretxe, Gaskon</creatorcontrib><creatorcontrib>Worthley, Daniel L</creatorcontrib><creatorcontrib>Woods, Susan L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ichinose, Mari</au><au>Suzuki, Nobumi</au><au>Wang, Tongtong</au><au>Wright, Josephine A</au><au>Lannagan, Tamsin R M</au><au>Vrbanac, Laura</au><au>Kobayashi, Hiroki</au><au>Gieniec, Krystyna A</au><au>Ng, Jia Q</au><au>Hayakawa, Yoku</au><au>García-Gallastegui, Patricia</au><au>Monsalve, Eva M</au><au>Bauer, Steven R</au><au>Laborda, Jorge</au><au>García-Ramírez, J J</au><au>Ibarretxe, Gaskon</au><au>Worthley, Daniel L</au><au>Woods, Susan L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>320</volume><issue>4</issue><spage>G506</spage><epage>G520</epage><pages>G506-G520</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><abstract>The stem/progenitor cells of the developing intestine are biologically distinct from their adult counterparts. Here, we examine the microenvironmental cues that regulate the embryonic stem/progenitor population, focusing on the role of Notch pathway factor delta-like protein-1 (DLK1). mRNA-seq analyses of intestinal mesenchymal cells (IMCs) collected from embryonic day 14.5 (E14.5) or adult IMCs and a novel coculture system with E14.5 intestinal epithelial organoids were used. Following addition of recombinant DLK1 (rDLK) or
siRNA (
), epithelial characteristics were compared using imaging, replating efficiency assays, qPCR, and immunocytochemistry. The intestinal phenotypes of littermate
and
mice were compared using immunohistochemistry. Using transcriptomic analyses, we identified morphogens derived from the embryonic mesenchyme that potentially regulate the developing epithelial cells, to focus on Notch family candidate DLK1. Immunohistochemistry indicated that DLK1 was expressed exclusively in the intestinal stroma at E14.5 at the top of emerging villi, decreased after birth, and shifted to the intestinal epithelium in adulthood. In coculture experiments, addition of rDLK1 to adult IMCs inhibited organoid differentiation, whereas
knockdown in embryonic IMCs increased epithelial differentiation to secretory lineage cells.
mice had restricted Ki67
cells in the villi base and increased secretory lineage cells compared with
embryos. Mesenchyme-derived DLK1 plays an important role in the promotion of epithelial stem/precursor expansion and prevention of differentiation to secretory lineages in the developing intestine.
Using a novel coculture system, transcriptomics, and transgenic mice, we investigated differential molecular signaling between the intestinal epithelium and mesenchyme during development and in the adult. We show that the Notch pathway factor delta-like protein-1 (DLK1) is stromally produced during development and uncover a new role for DLK1 in the regulation of intestinal epithelial stem/precursor expansion and differentiation to secretory lineages.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>33470182</pmid><doi>10.1152/ajpgi.00445.2020</doi><orcidid>https://orcid.org/0000-0002-3988-2499</orcidid><orcidid>https://orcid.org/0000-0002-8955-2017</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0193-1857 |
| ispartof | American journal of physiology: Gastrointestinal and liver physiology, 2021-04, Vol.320 (4), p.G506-G520 |
| issn | 0193-1857 1522-1547 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2479421259 |
| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Calcium-Binding Proteins - deficiency Calcium-Binding Proteins - genetics Calcium-Binding Proteins - metabolism Cell Communication Cell Differentiation Cell Lineage Cell Proliferation Cells, Cultured Coculture Techniques Embryo cells Embryonic Stem Cells - enzymology Epithelial cells Epithelial Cells - enzymology Epithelium Gene Expression Regulation, Developmental Immunocytochemistry Immunohistochemistry Intestinal Mucosa - embryology Intestinal Mucosa - enzymology Intestine Mesenchyme Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Organoids Phenotypes Preadipocyte factor 1 Progenitor cells Secretory Pathway Signal Transduction siRNA Stem Cell Niche Stem cells Stroma Stromal Cells - enzymology Transcriptome |
| title | Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T12%3A06%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Stromal%20DLK1%20promotes%20proliferation%20and%20inhibits%20differentiation%20of%20the%20intestinal%20epithelium%20during%20development&rft.jtitle=American%20journal%20of%20physiology:%20Gastrointestinal%20and%20liver%20physiology&rft.au=Ichinose,%20Mari&rft.date=2021-04-01&rft.volume=320&rft.issue=4&rft.spage=G506&rft.epage=G520&rft.pages=G506-G520&rft.issn=0193-1857&rft.eissn=1522-1547&rft_id=info:doi/10.1152/ajpgi.00445.2020&rft_dat=%3Cproquest_cross%3E2518415522%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2518415522&rft_id=info:pmid/33470182&rfr_iscdi=true |