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  • Lu, WS (author)

PDGFD switches on stem cell endothelial commitment

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-07-20
  • Springer Science and Business Media LLC,2022

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:150255804
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:150255804URI
  • https://doi.org/10.1007/s10456-022-09847-4DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Xu, PP (author)
  • Deng, BX (author)
  • Zhang, JN (author)
  • Zhan, Y (author)
  • Lin, XC (author)
  • Xu, XZ (author)
  • Xia, ZX (author)
  • Yang, XX (author)
  • Zeng, XL (author)
  • Huang, LJ (author)
  • Xie, BB (author)
  • Wang, CH (author)
  • Wang, SS (author)
  • Kuang, HQ (author)
  • Han, XJ (author)
  • Mora, A (author)
  • Cao, YHKarolinska Institutet (author)
  • Jiang, Q (author)
  • Li, XR (author)
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Angiogenesis: Springer Science and Business Media LLC25:4, s. 517-5331573-72090969-6970

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