The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation
Abstract Nucleosome assembly proteins (NAPs) are histone chaperones with an important role in chromatin structure and epigenetic regulation of gene expression. We find that high gene expression levels of mouse Nap1l3 are restricted to haematopoietic stem cells (HSCs) in mice. Importantly, with shRNA...
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2018
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oai:doaj.org-article:e85ae0005d43458ea0e54cc10c6d246f2021-12-02T15:08:22ZThe histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation10.1038/s41598-018-29518-z2045-2322https://doaj.org/article/e85ae0005d43458ea0e54cc10c6d246f2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29518-zhttps://doaj.org/toc/2045-2322Abstract Nucleosome assembly proteins (NAPs) are histone chaperones with an important role in chromatin structure and epigenetic regulation of gene expression. We find that high gene expression levels of mouse Nap1l3 are restricted to haematopoietic stem cells (HSCs) in mice. Importantly, with shRNA or CRISPR-Cas9 mediated loss of function of mouse Nap1l3 and with overexpression of the gene, the number of colony-forming cells and myeloid progenitor cells in vitro are reduced. This manifests as a striking decrease in the number of HSCs, which reduces their reconstituting activities in vivo. Downregulation of human NAP1L3 in umbilical cord blood (UCB) HSCs impairs the maintenance and proliferation of HSCs both in vitro and in vivo. NAP1L3 downregulation in UCB HSCs causes an arrest in the G0 phase of cell cycle progression and induces gene expression signatures that significantly correlate with downregulation of gene sets involved in cell cycle regulation, including E2F and MYC target genes. Moreover, we demonstrate that HOXA3 and HOXA5 genes are markedly upregulated when NAP1L3 is suppressed in UCB HSCs. Taken together, our findings establish an important role for NAP1L3 in HSC homeostasis and haematopoietic differentiation.Yaser HeshmatiShabnam KharaziGözde TürközDavid ChangEsmat Kamali DolatabadiJohan BoströmAleksandra KrsticTheodora BoukouraEmma WagnerNadir KadriRobert MånssonMikael AltunHong QianJulian WalfridssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-17 (2018) |
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Medicine R Science Q |
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Medicine R Science Q Yaser Heshmati Shabnam Kharazi Gözde Türköz David Chang Esmat Kamali Dolatabadi Johan Boström Aleksandra Krstic Theodora Boukoura Emma Wagner Nadir Kadri Robert Månsson Mikael Altun Hong Qian Julian Walfridsson The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation |
| description |
Abstract Nucleosome assembly proteins (NAPs) are histone chaperones with an important role in chromatin structure and epigenetic regulation of gene expression. We find that high gene expression levels of mouse Nap1l3 are restricted to haematopoietic stem cells (HSCs) in mice. Importantly, with shRNA or CRISPR-Cas9 mediated loss of function of mouse Nap1l3 and with overexpression of the gene, the number of colony-forming cells and myeloid progenitor cells in vitro are reduced. This manifests as a striking decrease in the number of HSCs, which reduces their reconstituting activities in vivo. Downregulation of human NAP1L3 in umbilical cord blood (UCB) HSCs impairs the maintenance and proliferation of HSCs both in vitro and in vivo. NAP1L3 downregulation in UCB HSCs causes an arrest in the G0 phase of cell cycle progression and induces gene expression signatures that significantly correlate with downregulation of gene sets involved in cell cycle regulation, including E2F and MYC target genes. Moreover, we demonstrate that HOXA3 and HOXA5 genes are markedly upregulated when NAP1L3 is suppressed in UCB HSCs. Taken together, our findings establish an important role for NAP1L3 in HSC homeostasis and haematopoietic differentiation. |
| format |
article |
| author |
Yaser Heshmati Shabnam Kharazi Gözde Türköz David Chang Esmat Kamali Dolatabadi Johan Boström Aleksandra Krstic Theodora Boukoura Emma Wagner Nadir Kadri Robert Månsson Mikael Altun Hong Qian Julian Walfridsson |
| author_facet |
Yaser Heshmati Shabnam Kharazi Gözde Türköz David Chang Esmat Kamali Dolatabadi Johan Boström Aleksandra Krstic Theodora Boukoura Emma Wagner Nadir Kadri Robert Månsson Mikael Altun Hong Qian Julian Walfridsson |
| author_sort |
Yaser Heshmati |
| title |
The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation |
| title_short |
The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation |
| title_full |
The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation |
| title_fullStr |
The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation |
| title_full_unstemmed |
The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation |
| title_sort |
histone chaperone nap1l3 is required for haematopoietic stem cell maintenance and differentiation |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/e85ae0005d43458ea0e54cc10c6d246f |
| work_keys_str_mv |
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