BMP signaling is required for postnatal murine hematopoietic stem cell self-renewal

Sarah Warsi, Ulrika Blank, Maria Dahl, Tan Hooi Min Grahn, Ludwig Schmiderer, Silja Andradottir, Stefan Karlsson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

2 Citeringar (SciVal)

Sammanfattning

Life-long production of blood from hematopoietic stem cells (HSC) is a process of strict modulation. Intrinsic and extrinsic signals govern fate options like self-renewal – a cardinal feature of HSC. Bone morphogenetic proteins (BMP) have an established role in embryonic hematopoiesis, but less is known about its functions in adulthood. Previously, SMAD-mediated BMP signaling has been proven dispensable for HSC. However, the BMP type-II receptor (BMPR-II) is highly expressed in HSC, leaving the possibility that BMP function via alternative pathways. Here, we establish that BMP signaling is required for self-renewal of adult HSC. Through conditional knockout we show that BMPR-II deficient HSC have impaired self-renewal and regenerative capacity. BMPR-II deficient cells have reduced p38 activation, implying that non-SMAD pathways operate downstream of BMP in HSC. Indeed, a majority of primitive hematopoietic cells do not engage in SMAD-mediated responses downstream of BMP in vivo. Furthermore, deficiency of BMPR-II results in increased expression of TJP1, a known regulator of self-renewal in other stem cells, and knockdown of TJP1 in primitive hematopoietic cells partly rescues the BMPR-II null phenotype. This suggests TJP1 may be a universal stem cell regulator. In conclusion, BMP signaling, in part mediated through TJP1, is required endogenously by adult HSC to maintain self-renewal capacity and proper resilience of the hematopoietic system during regeneration.

Originalspråkengelska
Sidor (från-till)2203-2214
Antal sidor12
TidskriftHaematologica
Volym106
Utgåva8
DOI
StatusPublished - 2021 aug.

Ämnesklassifikation (UKÄ)

  • Hematologi
  • Cell- och molekylärbiologi

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