Academic Journal
View in EDS

IRAK4 constrains cellular plasticity during chemically-induced cell fate reprogramming into multiple lineages.

Bibliographic Details
Title: IRAK4 constrains cellular plasticity during chemically-induced cell fate reprogramming into multiple lineages.
Authors: Huang C; Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. huangchuanshu@ojlab.AC.cn.; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325035, China. huangchuanshu@ojlab.AC.cn., Han X; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325035, China., Wang T; Key Laboratory of Laboratory Medicine, Ministry of Education, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Zhao Y; State Key Laboratory of Natural and Biomimetic Drugs, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100871, China. yangzhao@pku.edu.cn., Li J; Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. jun.li@wmu.edu.cn.; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325035, China. jun.li@wmu.edu.cn.
Source: EMBO reports [EMBO Rep] 2026 Aug; Vol. 27 (16), pp. 4903-4934. Date of Electronic Publication: 2026 Jul 15.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
Imprint Name(s): Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000-
MeSH Terms: Cellular Reprogramming*/drug effects , Cellular Reprogramming*/genetics , Interleukin-1 Receptor-Associated Kinases*/metabolism , Interleukin-1 Receptor-Associated Kinases*/genetics , Interleukin-1 Receptor-Associated Kinases*/antagonists & inhibitors , Cell Lineage*/drug effects , Cell Plasticity*/genetics , Cell Plasticity*/drug effects, Fibroblasts/cytology ; Fibroblasts/metabolism ; Fibroblasts/drug effects ; Hepatocytes/cytology ; Hepatocytes/metabolism ; Endoderm/cytology ; Endoderm/metabolism ; Neurons/cytology ; Neurons/metabolism ; Animals ; Mice ; Cell Cycle ; Cell Differentiation
Abstract: Chemical reprogramming holds transformative potential for regenerative medicine. However, the regulatory mechanisms governing cell fate transitions are not well understood. Here, we identify Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a barrier to multi-lineage reprogramming. Pharmacological inhibition of IRAK4 enhances the reprogramming of mouse embryonic fibroblasts (MEFs) through a chemically activated multi-lineage priming (CaMP) state and extraembryonic endoderm (XEN)-like intermediates, increasing colony formation, and the expression of core XEN regulators (Sox17, Gata4, Sall4, and Foxa2). Genetic knockdown of Irak4 similarly accelerates reprogramming, whereas its overexpression blocks cell fate transitions. IRAK4 inhibition enhances chromatin accessibility and reshapes cell cycle dynamics, characterized by G0/G1 shortening and G2/M lengthening, potentially contributing to multi-lineage state establishment. Furthermore, IRAK4 suppression enhances the direct conversion of MEFs to neuron-like and hepatocyte-like cells, which exhibit enhanced functional maturity, including increased glycogen storage and improved detoxification capacity. Our findings establish IRAK4 as a regulator that constrains cellular plasticity potentially by coordinating chromatin accessibility and cell cycle dynamics.
(© 2026. The Author(s).)
Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests.
References: Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: 34557778)
J Med Chem. 2017 Jul 13;60(13):5521-5542. (PMID: 28498658)
Nat Biotechnol. 2019 Aug;37(8):907-915. (PMID: 31375807)
Cell. 2012 Mar 16;148(6):1110-22. (PMID: 22424223)
Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8912-7. (PMID: 19447925)
Nat Chem Biol. 2025 Jul;21(7):1030-1038. (PMID: 39753706)
Genes Dev. 2009 Sep 15;23(18):2134-9. (PMID: 19696146)
PLoS Biol. 2008 Oct 21;6(10):e253. (PMID: 18942890)
Nucleic Acids Res. 2025 Jan 6;53(D1):D1670-D1676. (PMID: 39470721)
Curr Top Med Chem. 2009;9(8):724-37. (PMID: 19689377)
Hepatology. 2023 May 1;77(5):1550-1565. (PMID: 35881538)
Cell Stem Cell. 2011 Dec 2;9(6):575-87. (PMID: 22100412)
Nature. 2009 Aug 27;460(7259):1149-53. (PMID: 19668189)
Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677)
Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5. (PMID: 27079975)
Nat Cell Biol. 2023 Aug;25(8):1146-1156. (PMID: 37550515)
Nat Commun. 2025 Apr 30;16(1):4054. (PMID: 40307238)
Cell. 2006 Aug 25;126(4):663-76. (PMID: 16904174)
Cell Stem Cell. 2018 Apr 5;22(4):529-542.e5. (PMID: 29625068)
Cell Stem Cell. 2010 Jan 8;6(1):71-9. (PMID: 20036631)
Biochem Pharmacol. 2010 Dec 15;80(12):1981-91. (PMID: 20599782)
Curr Biol. 2009 Nov 3;19(20):1718-23. (PMID: 19765992)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nature. 2009 Aug 27;460(7259):1140-4. (PMID: 19668186)
Nat Rev Mol Cell Biol. 2021 Jun;22(6):410-424. (PMID: 33619373)
Nature. 2009 Aug 27;460(7259):1145-8. (PMID: 19668190)
Curr Biol. 2011 Jan 11;21(1):45-52. (PMID: 21167714)
Nat Commun. 2026 Jan 30;17(1):. (PMID: 41617717)
Cell Stem Cell. 2009 Nov 6;5(5):491-503. (PMID: 19818703)
Front Cell Dev Biol. 2022 Mar 25;10:865038. (PMID: 35399519)
Adv Sci (Weinh). 2025 Aug;12(32):e15528. (PMID: 40448624)
Nature. 2009 Aug 27;460(7259):1132-5. (PMID: 19668191)
Bioorg Med Chem Lett. 2017 Jun 15;27(12):2721-2726. (PMID: 28501511)
Cell. 2026 Jun 11;189(12):3541-3552.e18. (PMID: 41999746)
Cell Stem Cell. 2010 Dec 3;7(6):651-5. (PMID: 21112560)
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3291-5. (PMID: 18482836)
Cell Stem Cell. 2020 Oct 1;27(4):523-531. (PMID: 33007237)
Nat Methods. 2009 Nov;6(11):805-8. (PMID: 19838168)
Science. 2013 Aug 9;341(6146):651-4. (PMID: 23868920)
Genome Biol. 2008;9(9):R137. (PMID: 18798982)
Cell. 2015 Dec 17;163(7):1678-91. (PMID: 26686652)
Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286)
Nat Biotechnol. 2008 Jul;26(7):795-7. (PMID: 18568017)
Cell Stem Cell. 2025 Apr 03;32(4):613-626.e8. (PMID: 40054463)
Mol Cell. 2010 May 28;38(4):576-89. (PMID: 20513432)
Nat Cell Biol. 2018 May;20(5):620-631. (PMID: 29686265)
Nature. 2022 May;605(7909):325-331. (PMID: 35418683)
Cell Stem Cell. 2010 Nov 5;7(5):565-70. (PMID: 21040898)
Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943)
Cell Stem Cell. 2023 Sep 7;30(9):1130-1147. (PMID: 37625410)
Commun Biol. 2020 Oct 30;3(1):629. (PMID: 33128002)
Cell Stem Cell. 2017 Aug 3;21(2):264-273.e7. (PMID: 28648365)
Cell Rep. 2023 Jun 27;42(6):112566. (PMID: 37235474)
Cell Stem Cell. 2023 Apr 6;30(4):450-459.e9. (PMID: 36944335)
Cell Rep. 2016 Apr 26;15(4):814-829. (PMID: 27149847)
Cell. 2015 Jul 30;162(3):564-79. (PMID: 26232226)
Cell Stem Cell. 2018 Jul 05;23(1):31-45.e7. (PMID: 29937202)
Stem Cells. 2010 Apr;28(4):721-33. (PMID: 20201066)
Curr Opin Genet Dev. 2019 Apr;55:1-10. (PMID: 31103921)
Grant Information: 32400603 MOST | National Natural Science Foundation of China (NSFC); LQ24H110004 MOST | NSFC | NSFC-Zhejiang Joint Fund | | Natural Science Foundation of Zhejiang Province (ZJNSF); KYYW202319 and KYYW202401 Fundamental Research Foundation of wenzhou medical university
Substance Nomenclature: EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
Entry Date(s): Date Created: 20260715 Date Completed: 20260825 Latest Revision: 20260903
Update Code: 20260903
PubMed Central ID: PMC13503836
DOI: 10.1038/s44319-026-00855-9
PMID: 42458070
Database: MEDLINE
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://dx.doi.org/doi:10.1038/s44319-026-00855-9
    Name: EDS - Springer Nature Journals (s7799221)
    Category: fullText
    Text: View record at Springer
  – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=14693178&ISBN=&volume=27&issue=16&date=20260801&spage=4903&pages=4903-4934&title=EMBO reports&atitle=IRAK4%20constrains%20cellular%20plasticity%20during%20chemically-induced%20cell%20fate%20reprogramming%20into%20multiple%20lineages.&aulast=Huang%20C&id=DOI:10.1038/s44319-026-00855-9
    Name: Full Text Finder (for New FTF UI) (ns324271)
    Category: fullText
    Text: Full Text Finder
    MouseOverText: Full Text Finder
Header DbId: cmedm
DbLabel: MEDLINE
An: 42458070
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: IRAK4 constrains cellular plasticity during chemically-induced cell fate reprogramming into multiple lineages.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Huang+C%22">Huang C</searchLink>; Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. huangchuanshu@ojlab.AC.cn.; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325035, China. huangchuanshu@ojlab.AC.cn.<br /><searchLink fieldCode="AU" term="%22Han+X%22">Han X</searchLink>; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325035, China.<br /><searchLink fieldCode="AU" term="%22Wang+T%22">Wang T</searchLink>; Key Laboratory of Laboratory Medicine, Ministry of Education, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.<br /><searchLink fieldCode="AU" term="%22Zhao+Y%22">Zhao Y</searchLink>; State Key Laboratory of Natural and Biomimetic Drugs, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100871, China. yangzhao@pku.edu.cn.<br /><searchLink fieldCode="AU" term="%22Li+J%22">Li J</searchLink>; Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. jun.li@wmu.edu.cn.; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325035, China. jun.li@wmu.edu.cn.
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22100963049%22">EMBO reports</searchLink> [EMBO Rep] 2026 Aug; Vol. 27 (16), pp. 4903-4934. <i>Date of Electronic Publication: </i>2026 Jul 15.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Nature+Publishing+Group%22">Nature Publishing Group </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>100963049 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1469-3178 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%221469221X%22">1469221X </searchLink><i>NLM ISO Abbreviation: </i>EMBO Rep <i>Subsets: </i>MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: <i>Publication</i>: 2024- : [London] : Nature Publishing Group<br /><i>Original Publication</i>: Oxford, UK : Published for EMBO by Oxford University Press, 2000-
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Cellular+Reprogramming%22">Cellular Reprogramming*</searchLink>/<searchLink fieldCode="MM" term="%22Cellular+Reprogramming+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Cellular+Reprogramming%22">Cellular Reprogramming*</searchLink>/<searchLink fieldCode="MM" term="%22Cellular+Reprogramming+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Interleukin-1+Receptor-Associated+Kinases%22">Interleukin-1 Receptor-Associated Kinases*</searchLink>/<searchLink fieldCode="MM" term="%22Interleukin-1+Receptor-Associated+Kinases+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Interleukin-1+Receptor-Associated+Kinases%22">Interleukin-1 Receptor-Associated Kinases*</searchLink>/<searchLink fieldCode="MM" term="%22Interleukin-1+Receptor-Associated+Kinases+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Interleukin-1+Receptor-Associated+Kinases%22">Interleukin-1 Receptor-Associated Kinases*</searchLink>/<searchLink fieldCode="MM" term="%22Interleukin-1+Receptor-Associated+Kinases+antagonists+%26+inhibitors%22">antagonists & inhibitors</searchLink> <br /><searchLink fieldCode="MM" term="%22Cell+Lineage%22">Cell Lineage*</searchLink>/<searchLink fieldCode="MM" term="%22Cell+Lineage+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Cell+Plasticity%22">Cell Plasticity*</searchLink>/<searchLink fieldCode="MM" term="%22Cell+Plasticity+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Cell+Plasticity%22">Cell Plasticity*</searchLink>/<searchLink fieldCode="MM" term="%22Cell+Plasticity+drug+effects%22">drug effects</searchLink><br /><searchLink fieldCode="MH" term="%22Fibroblasts%22">Fibroblasts</searchLink>/<searchLink fieldCode="MH" term="%22Fibroblasts+cytology%22">cytology</searchLink> ; <searchLink fieldCode="MH" term="%22Fibroblasts%22">Fibroblasts</searchLink>/<searchLink fieldCode="MH" term="%22Fibroblasts+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Fibroblasts%22">Fibroblasts</searchLink>/<searchLink fieldCode="MH" term="%22Fibroblasts+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Hepatocytes%22">Hepatocytes</searchLink>/<searchLink fieldCode="MH" term="%22Hepatocytes+cytology%22">cytology</searchLink> ; <searchLink fieldCode="MH" term="%22Hepatocytes%22">Hepatocytes</searchLink>/<searchLink fieldCode="MH" term="%22Hepatocytes+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Endoderm%22">Endoderm</searchLink>/<searchLink fieldCode="MH" term="%22Endoderm+cytology%22">cytology</searchLink> ; <searchLink fieldCode="MH" term="%22Endoderm%22">Endoderm</searchLink>/<searchLink fieldCode="MH" term="%22Endoderm+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Neurons%22">Neurons</searchLink>/<searchLink fieldCode="MH" term="%22Neurons+cytology%22">cytology</searchLink> ; <searchLink fieldCode="MH" term="%22Neurons%22">Neurons</searchLink>/<searchLink fieldCode="MH" term="%22Neurons+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Cell+Cycle%22">Cell Cycle</searchLink> ; <searchLink fieldCode="MH" term="%22Cell+Differentiation%22">Cell Differentiation</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Chemical reprogramming holds transformative potential for regenerative medicine. However, the regulatory mechanisms governing cell fate transitions are not well understood. Here, we identify Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a barrier to multi-lineage reprogramming. Pharmacological inhibition of IRAK4 enhances the reprogramming of mouse embryonic fibroblasts (MEFs) through a chemically activated multi-lineage priming (CaMP) state and extraembryonic endoderm (XEN)-like intermediates, increasing colony formation, and the expression of core XEN regulators (Sox17, Gata4, Sall4, and Foxa2). Genetic knockdown of Irak4 similarly accelerates reprogramming, whereas its overexpression blocks cell fate transitions. IRAK4 inhibition enhances chromatin accessibility and reshapes cell cycle dynamics, characterized by G0/G1 shortening and G2/M lengthening, potentially contributing to multi-lineage state establishment. Furthermore, IRAK4 suppression enhances the direct conversion of MEFs to neuron-like and hepatocyte-like cells, which exhibit enhanced functional maturity, including increased glycogen storage and improved detoxification capacity. Our findings establish IRAK4 as a regulator that constrains cellular plasticity potentially by coordinating chromatin accessibility and cell cycle dynamics.<br /> (© 2026. The Author(s).)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Disclosure and competing interests statement. The authors declare no competing interests.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: <searchLink fieldCode="PM" term="%2234557778%22">34557778)</searchLink><br />J Med Chem. 2017 Jul 13;60(13):5521-5542. (PMID: <searchLink fieldCode="PM" term="%2228498658%22">28498658)</searchLink><br />Nat Biotechnol. 2019 Aug;37(8):907-915. (PMID: <searchLink fieldCode="PM" term="%2231375807%22">31375807)</searchLink><br />Cell. 2012 Mar 16;148(6):1110-22. (PMID: <searchLink fieldCode="PM" term="%2222424223%22">22424223)</searchLink><br />Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8912-7. (PMID: <searchLink fieldCode="PM" term="%2219447925%22">19447925)</searchLink><br />Nat Chem Biol. 2025 Jul;21(7):1030-1038. (PMID: <searchLink fieldCode="PM" term="%2239753706%22">39753706)</searchLink><br />Genes Dev. 2009 Sep 15;23(18):2134-9. (PMID: <searchLink fieldCode="PM" term="%2219696146%22">19696146)</searchLink><br />PLoS Biol. 2008 Oct 21;6(10):e253. (PMID: <searchLink fieldCode="PM" term="%2218942890%22">18942890)</searchLink><br />Nucleic Acids Res. 2025 Jan 6;53(D1):D1670-D1676. (PMID: <searchLink fieldCode="PM" term="%2239470721%22">39470721)</searchLink><br />Curr Top Med Chem. 2009;9(8):724-37. (PMID: <searchLink fieldCode="PM" term="%2219689377%22">19689377)</searchLink><br />Hepatology. 2023 May 1;77(5):1550-1565. (PMID: <searchLink fieldCode="PM" term="%2235881538%22">35881538)</searchLink><br />Cell Stem Cell. 2011 Dec 2;9(6):575-87. (PMID: <searchLink fieldCode="PM" term="%2222100412%22">22100412)</searchLink><br />Nature. 2009 Aug 27;460(7259):1149-53. (PMID: <searchLink fieldCode="PM" term="%2219668189%22">19668189)</searchLink><br />Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: <searchLink fieldCode="PM" term="%2224227677%22">24227677)</searchLink><br />Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5. (PMID: <searchLink fieldCode="PM" term="%2227079975%22">27079975)</searchLink><br />Nat Cell Biol. 2023 Aug;25(8):1146-1156. (PMID: <searchLink fieldCode="PM" term="%2237550515%22">37550515)</searchLink><br />Nat Commun. 2025 Apr 30;16(1):4054. (PMID: <searchLink fieldCode="PM" term="%2240307238%22">40307238)</searchLink><br />Cell. 2006 Aug 25;126(4):663-76. (PMID: <searchLink fieldCode="PM" term="%2216904174%22">16904174)</searchLink><br />Cell Stem Cell. 2018 Apr 5;22(4):529-542.e5. (PMID: <searchLink fieldCode="PM" term="%2229625068%22">29625068)</searchLink><br />Cell Stem Cell. 2010 Jan 8;6(1):71-9. (PMID: <searchLink fieldCode="PM" term="%2220036631%22">20036631)</searchLink><br />Biochem Pharmacol. 2010 Dec 15;80(12):1981-91. (PMID: <searchLink fieldCode="PM" term="%2220599782%22">20599782)</searchLink><br />Curr Biol. 2009 Nov 3;19(20):1718-23. (PMID: <searchLink fieldCode="PM" term="%2219765992%22">19765992)</searchLink><br />Genome Biol. 2014;15(12):550. (PMID: <searchLink fieldCode="PM" term="%2225516281%22">25516281)</searchLink><br />Nature. 2009 Aug 27;460(7259):1140-4. (PMID: <searchLink fieldCode="PM" term="%2219668186%22">19668186)</searchLink><br />Nat Rev Mol Cell Biol. 2021 Jun;22(6):410-424. (PMID: <searchLink fieldCode="PM" term="%2233619373%22">33619373)</searchLink><br />Nature. 2009 Aug 27;460(7259):1145-8. (PMID: <searchLink fieldCode="PM" term="%2219668190%22">19668190)</searchLink><br />Curr Biol. 2011 Jan 11;21(1):45-52. (PMID: <searchLink fieldCode="PM" term="%2221167714%22">21167714)</searchLink><br />Nat Commun. 2026 Jan 30;17(1):. (PMID: <searchLink fieldCode="PM" term="%2241617717%22">41617717)</searchLink><br />Cell Stem Cell. 2009 Nov 6;5(5):491-503. (PMID: <searchLink fieldCode="PM" term="%2219818703%22">19818703)</searchLink><br />Front Cell Dev Biol. 2022 Mar 25;10:865038. (PMID: <searchLink fieldCode="PM" term="%2235399519%22">35399519)</searchLink><br />Adv Sci (Weinh). 2025 Aug;12(32):e15528. (PMID: <searchLink fieldCode="PM" term="%2240448624%22">40448624)</searchLink><br />Nature. 2009 Aug 27;460(7259):1132-5. (PMID: <searchLink fieldCode="PM" term="%2219668191%22">19668191)</searchLink><br />Bioorg Med Chem Lett. 2017 Jun 15;27(12):2721-2726. (PMID: <searchLink fieldCode="PM" term="%2228501511%22">28501511)</searchLink><br />Cell. 2026 Jun 11;189(12):3541-3552.e18. (PMID: <searchLink fieldCode="PM" term="%2241999746%22">41999746)</searchLink><br />Cell Stem Cell. 2010 Dec 3;7(6):651-5. (PMID: <searchLink fieldCode="PM" term="%2221112560%22">21112560)</searchLink><br />Bioorg Med Chem Lett. 2008 Jun 1;18(11):3291-5. (PMID: <searchLink fieldCode="PM" term="%2218482836%22">18482836)</searchLink><br />Cell Stem Cell. 2020 Oct 1;27(4):523-531. (PMID: <searchLink fieldCode="PM" term="%2233007237%22">33007237)</searchLink><br />Nat Methods. 2009 Nov;6(11):805-8. (PMID: <searchLink fieldCode="PM" term="%2219838168%22">19838168)</searchLink><br />Science. 2013 Aug 9;341(6146):651-4. (PMID: <searchLink fieldCode="PM" term="%2223868920%22">23868920)</searchLink><br />Genome Biol. 2008;9(9):R137. (PMID: <searchLink fieldCode="PM" term="%2218798982%22">18798982)</searchLink><br />Cell. 2015 Dec 17;163(7):1678-91. (PMID: <searchLink fieldCode="PM" term="%2226686652%22">26686652)</searchLink><br />Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: <searchLink fieldCode="PM" term="%2222388286%22">22388286)</searchLink><br />Nat Biotechnol. 2008 Jul;26(7):795-7. (PMID: <searchLink fieldCode="PM" term="%2218568017%22">18568017)</searchLink><br />Cell Stem Cell. 2025 Apr 03;32(4):613-626.e8. (PMID: <searchLink fieldCode="PM" term="%2240054463%22">40054463)</searchLink><br />Mol Cell. 2010 May 28;38(4):576-89. (PMID: <searchLink fieldCode="PM" term="%2220513432%22">20513432)</searchLink><br />Nat Cell Biol. 2018 May;20(5):620-631. (PMID: <searchLink fieldCode="PM" term="%2229686265%22">29686265)</searchLink><br />Nature. 2022 May;605(7909):325-331. (PMID: <searchLink fieldCode="PM" term="%2235418683%22">35418683)</searchLink><br />Cell Stem Cell. 2010 Nov 5;7(5):565-70. (PMID: <searchLink fieldCode="PM" term="%2221040898%22">21040898)</searchLink><br />Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: <searchLink fieldCode="PM" term="%2219505943%22">19505943)</searchLink><br />Cell Stem Cell. 2023 Sep 7;30(9):1130-1147. (PMID: <searchLink fieldCode="PM" term="%2237625410%22">37625410)</searchLink><br />Commun Biol. 2020 Oct 30;3(1):629. (PMID: <searchLink fieldCode="PM" term="%2233128002%22">33128002)</searchLink><br />Cell Stem Cell. 2017 Aug 3;21(2):264-273.e7. (PMID: <searchLink fieldCode="PM" term="%2228648365%22">28648365)</searchLink><br />Cell Rep. 2023 Jun 27;42(6):112566. (PMID: <searchLink fieldCode="PM" term="%2237235474%22">37235474)</searchLink><br />Cell Stem Cell. 2023 Apr 6;30(4):450-459.e9. (PMID: <searchLink fieldCode="PM" term="%2236944335%22">36944335)</searchLink><br />Cell Rep. 2016 Apr 26;15(4):814-829. (PMID: <searchLink fieldCode="PM" term="%2227149847%22">27149847)</searchLink><br />Cell. 2015 Jul 30;162(3):564-79. (PMID: <searchLink fieldCode="PM" term="%2226232226%22">26232226)</searchLink><br />Cell Stem Cell. 2018 Jul 05;23(1):31-45.e7. (PMID: <searchLink fieldCode="PM" term="%2229937202%22">29937202)</searchLink><br />Stem Cells. 2010 Apr;28(4):721-33. (PMID: <searchLink fieldCode="PM" term="%2220201066%22">20201066)</searchLink><br />Curr Opin Genet Dev. 2019 Apr;55:1-10. (PMID: <searchLink fieldCode="PM" term="%2231103921%22">31103921)</searchLink>
– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: 32400603 MOST | National Natural Science Foundation of China (NSFC); LQ24H110004 MOST | NSFC | NSFC-Zhejiang Joint Fund | | Natural Science Foundation of Zhejiang Province (ZJNSF); KYYW202319 and KYYW202401 Fundamental Research Foundation of wenzhou medical university
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260715 <i>Date Completed: </i>20260825 <i>Latest Revision: </i>20260903
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260903
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC13503836
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1038/s44319-026-00855-9
– Name: AN
  Label: PMID
  Group: ID
  Data: 42458070
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42458070
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1038/s44319-026-00855-9
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 4903
    Subjects:
      – SubjectFull: Fibroblasts cytology
        Type: general
      – SubjectFull: Fibroblasts metabolism
        Type: general
      – SubjectFull: Fibroblasts drug effects
        Type: general
      – SubjectFull: Hepatocytes cytology
        Type: general
      – SubjectFull: Hepatocytes metabolism
        Type: general
      – SubjectFull: Endoderm cytology
        Type: general
      – SubjectFull: Endoderm metabolism
        Type: general
      – SubjectFull: Neurons cytology
        Type: general
      – SubjectFull: Neurons metabolism
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Cell Cycle
        Type: general
      – SubjectFull: Cell Differentiation
        Type: general
      – SubjectFull: Cellular Reprogramming drug effects
        Type: general
      – SubjectFull: Cellular Reprogramming genetics
        Type: general
      – SubjectFull: Interleukin-1 Receptor-Associated Kinases metabolism
        Type: general
      – SubjectFull: Interleukin-1 Receptor-Associated Kinases genetics
        Type: general
      – SubjectFull: Interleukin-1 Receptor-Associated Kinases antagonists & inhibitors
        Type: general
      – SubjectFull: Cell Lineage drug effects
        Type: general
      – SubjectFull: Cell Plasticity genetics
        Type: general
      – SubjectFull: Cell Plasticity drug effects
        Type: general
    Titles:
      – TitleFull: IRAK4 constrains cellular plasticity during chemically-induced cell fate reprogramming into multiple lineages.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Huang C
      – PersonEntity:
          Name:
            NameFull: Han X
      – PersonEntity:
          Name:
            NameFull: Wang T
      – PersonEntity:
          Name:
            NameFull: Zhao Y
      – PersonEntity:
          Name:
            NameFull: Li J
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 08
              Text: 2026 Aug
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1469-3178
          Numbering:
            – Type: volume
              Value: 27
            – Type: issue
              Value: 16
          Titles:
            – TitleFull: EMBO reports
              Type: main
ResultId 1