Scientists uncover the important role of bone marrow pluripotent progenitor cells in genetic disease

Recently, key laboratory researcher Wang Qianfei from Beijing Institute of Genomics, Chinese Academy of Medical accurate genome and professor Yang Fengchun of the University of Miami Miller School of Medicine cooperated to reveal the critical role of germline newborn Bohring-Opitz syndrome mutations ASXL1 multipotent progenitor cells in the bone marrow stromal function bone development and maintenance, and the research was published in the journal Stem Cell Reports. There are also some other studies about recombinant proteins that were published in the famous journal.

Bone marrow stromal multipotent progenitor cell (BMSC) is a kind of multipotent progenitor cells with self-renewal and multi-lineage differentiation potential. The relationship between ostosis and fat cells in BMSC is crucial for normal bone homeostasis and the differentiation fate of these cells causes the abnormalities of body. Bohring-Opitz syndrome (BOS) is heterogeneity of genetic disease which causes death of young children, and it is characterized by severe growth retardation, upper fixed contractures, abnormal posture, feeding difficulties and severe mental disorders. Previous studies have found that the patients showed germline mutations ASXL1 gene BOS newborn, resulting in loss of function protein ASXL1. However, as enhancer of transcriptional activation / inhibition key regulator PcG and TrxG protein, the cellular and molecular mechanisms of ASXL1 causing gene mutation and inducing BOS still remains unclear.

The researchers found in Asxl1-targeted mouse model that Asxl1 gene complete knockout and conditional knockout of osteoblast progenitor cells cause severe bone loss and reduction of the number of bone marrow stromal multipotent progenitor cells; Asxl1-knockout bone marrow stromal multipotent progenitor cells showed self-renewal ability damage and change of differentiation tend. Transcriptome sequencing and bioinformatics analysis showed that some gene expression related to cell proliferation, bone development and morphogenesis changed; moreover, imprinted gene enrichment analysis of gene expression down-regulation of self-renewal of stem cells, suggesting that Asxl1 has regulation function on the dryness of bone marrow stromal multipotent progenitor cells. The researchers further found that the re-expression of Asxl1 makes the expression of the dry genes NANOG and OCT4 normalized, restoring the self-renewal capacity of bone marrow stromal Asxl1 knockout pluripotent progenitor cells. Besides, taking suitable recombinant rat proteins or recombinant mouse proteins is very important.

ASXL1 somatic mutations occur in myeloid malignancies, including myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid leukemia. The study reveals that ASXL1 plays an important role in Bohring-Opitz Syndrome by affecting the bone marrow stromal multipotent progenitor cell function and bone development, providing new opportunities for metabolic bone disease and clinical treatment of cancer.