PMID- 33593142 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20211214 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 30 IP - 7 DP - 2021 Apr 1 TI - The Chromatin Remodeling Complex CHD1 Regulates the Primitive State of Mesenchymal Stromal Cells to Control Their Stem Cell Supporting Activity. PG - 363-373 LID - 10.1089/scd.2020.0166 [doi] AB - The primitive state (stemness) of mesenchymal stromal cells (MSCs) is responsible for supporting the function of tissue-specific stem cells to regenerate damaged tissues. However, molecular mechanisms regulating the stemness of MSCs remain unknown. In this study, we found that the primitive state of MSCs is hierarchically regulated by the expression levels of the chromatin remodeling complex, CHD1, with CHD1 expression levels higher in the undifferentiated state, and decreasing upon MSC differentiation. Consistently, CHD1 expression levels decrease during progressive loss of clonogenic progenitors (CFU-F) induced by passage cultures. Moreover, knockdown (KD) of CHD1 decreased CFU-F frequency, whereas CHD1 overexpression increased it. In addition, the expression of stem cell-specific genes was down- or upregulated upon KD or overexpression of CHD1, respectively, accompanied by associated changes in chromatin condensation. Importantly, altering CHD1 expression levels affected the ability of MSCs to support the self-renewing expansion of hematopoietic stem cells (HSCs). Furthermore, CHD1 levels were significantly decreased in MSCs from acute myeloid leukemia or aplastic anemia patients, where CFU-F and HSC-supporting activities are lost. Altogether, these findings show that chromatin remodeling by CHD1 is a molecular parameter that influences the primitive state of MSCs and their stem cell-supporting activity, which controls tissue regeneration. FAU - Lee, Hae-Ri AU - Lee HR AD - Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Yang, Seung-Jip AU - Yang SJ AD - Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Choi, Hyun-Kyung AU - Choi HK AD - Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Kim, Jin-A AU - Kim JA AD - Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Oh, Il-Hoan AU - Oh IH AD - Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (DNA-Binding Proteins) RN - EC 3.6.4.- (DNA Helicases) RN - EC 3.6.4.12 (CHD1 protein, human) SB - IM MH - Adipogenesis/genetics MH - Cell Differentiation/*genetics MH - Cell Proliferation/genetics MH - Cells, Cultured MH - Chromatin Assembly and Disassembly/*genetics MH - Coculture Techniques MH - DNA Helicases/*genetics/metabolism MH - DNA-Binding Proteins/*genetics/metabolism MH - Epithelial-Mesenchymal Transition/genetics MH - Fetal Blood/cytology MH - *Gene Expression Regulation MH - Hematopoietic Stem Cells/cytology/*metabolism MH - Humans MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Osteogenesis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction OTO - NOTNLM OT - chromatin remodeling OT - mesenchymal stromal cells OT - stemness EDAT- 2021/02/18 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/02/17 05:36 PHST- 2021/02/18 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/02/17 05:36 [entrez] AID - 10.1089/scd.2020.0166 [doi] PST - ppublish SO - Stem Cells Dev. 2021 Apr 1;30(7):363-373. doi: 10.1089/scd.2020.0166.