Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naive pluripotency under inhibition of protein kinase C

Dai, Yujian1; Sun, Jialei1; He, Na2; An, Liyou3; Hou, Chunhui4; Du, Fuliang1

2022-08-01

10.1038/s41420-022-01131-0

CELL DEATH DISCOVERY   Impact Factor & Quartile

2058-7716

The pluripotency of naive mouse embryonic stem cells (mES) is regulated by multiple signaling pathways, with inhibition of protein kinase C (PKCi) playing a particularly important role in maintaining naive mES. However, the regulatory function of nucleosome remodeling and deacetylase (NuRD) complex in mES cultured in a PKCi system is unknown. We found that, compared with 2iL-derived mES, PKCi-derived mES showed low mRNA expression of NuRD complex subunits, including MBD3, HDAC1/HDAC2, MTA1, and RbAP46/RbAP48. Western blot showed that PKCi-derived mES expressed lower protein levels of MBD3 and HDAC2 at passage 3, as well as MBD3, HDAC2, and MTA1 at passage 10, indicating that PKCi suppressed NuRD complex expression. Knockdown of MBD3 increased PKCi-derived mES pluripotency by increasing NANOG and OCT4 expression and colony formation. By contrast, overexpression of MBD3 or removal of PKC inhibitor-induced differentiation of mES, results in reduced NANOG, OCT4, and REX1 expression and colony formation, increased differentiation-related gene expression, and differentiation into flat cells. Knockdown of MBD3 in mES upon PKC inhibitor removal partially reversed cell differentiation. Our results show that the regulatory NuRD complex and its MBD3 subunit influence the naive pluripotency of mES cultured in a PKCi system.

SCI

English

Corresponding

Natural Science Foundation of China (NSFC)["31872353","32072732","31340041","31471388"] ; National Key R&D Program of China[2018YFC1004500] ; Stable Support Plan Program of Shenzhen Natural Science Fund[20200925153547003] ; Shenzhen Innovation Committee of Science and Technology[ZDSYS20200811144002008] ; Southern University of Science and Technology["G02226301","Y01501821"]

Cell Biology

Cell Biology

WOS:000834811500001

SPRINGERNATURE

Web of Science

1.Nanjing Normal Univ, Coll Life Sci, Jiangsu Key Lab Mol & Med Biotechnol, Nanjing 210046, Peoples R China
2.Harbin Inst Technol, Harbin 150001, Heilongjiang, Peoples R China
3.Xinjiang Univ, Coll Life Sci & Technol, Xinjiang Key Lab Biol Resources & Genet Engn, Urumqi 830046, Peoples R China
4.Southern Univ Sci & Technol, Sch Life Sci, Shenzhen Key Lab Gene Regulat & Syst Biol, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China

Dai, Yujian,Sun, Jialei,He, Na,et al. Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naive pluripotency under inhibition of protein kinase C[J]. CELL DEATH DISCOVERY,2022,8(1).

Dai, Yujian,Sun, Jialei,He, Na,An, Liyou,Hou, Chunhui,&Du, Fuliang.(2022).Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naive pluripotency under inhibition of protein kinase C.CELL DEATH DISCOVERY,8(1).

Dai, Yujian,et al."Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naive pluripotency under inhibition of protein kinase C".CELL DEATH DISCOVERY 8.1(2022).