Stem Cells and Regenerative Medicine
Human embryonic stem cells (hESCs) have a tremendous potential to be used for both therapeutic applications as well as for understanding basic biological processes. The potential to differentiate into any cell lineage and potential for unlimited cell division are unique characteristics of hESCs. We have discovered that this unlimited proliferative potential is linked to an abbreviated cell cycle; the embryonic stem cells have a shortened G1 phase of the cell cycle. This finding provides a paradigm to further explore cell growth regulatory mechanisms in the physiological context of pluripotency (see Cell Cycle, Cancer and Aging). We are examining mechanisms that mediate lengthening of the cell cycle and early stage of cell fate determination as pluripotent stem cells undergo differentiation.
In addition, we are examining osteogenic differentiation from mesenchymal stem cells to define the molecular basis of skeletal regenerative medicine (see Musculoskeletal Biology and Pathology).
Landmark Papers
Gordon JAR, Tye CE, Banerjee B, Ghule PN, van Wijnen AJ, Kabala FS, Page NA, Falcone MM, Stein JL, Stein GS, Lian JB. LINC01638 sustains human mesenchymal stem cell self-renewal and competency for osteogenic cell fate. Sci Rep. 2023 Nov 20;13(1):20314. doi: 10.1038/s41598-023-46202-z. PMID: 37985890; PMCID: PMC10662126.
Tye CE, Ghule PN, Gordon JAR, Kabala FS, Page NA, Falcone MM, Tracy KM, van Wijnen AJ, Stein JL, Lian JB, Stein GS. LncMIR181A1HG is a novel chromatin-bound epigenetic suppressor of early stage osteogenic lineage commitment. Sci Rep. 2022 May 11;12(1):7770. doi: 10.1038/s41598-022-11814-4. PMID: 35546168; PMCID: PMC9095685.
Fritz AJ, Hong D, Boyd J, Kost J, Finstaad KH, Fitzgerald MP, Hanna S, Abuarqoub AH, Malik M, Bushweller J, Tye C, Ghule P, Gordon J, Frietze S, Zaidi SK, Lian JB, Stein JL, Stein GS. RUNX1 and RUNX2 transcription factors function in opposing roles to regulate breast cancer stem cells. J Cell Physiol. 2020 Oct;235(10):7261-7272. doi: 10.1002/jcp.29625. Epub 2020 Mar 17. PMID: 32180230; PMCID: PMC7415511.
Hong D, Fritz AJ, Finstad KH, Fitzgerald MP, Weinheimer A, Viens AL, Ramsey J, Stein JL, Lian JB, Stein GS. Suppression of Breast Cancer Stem Cells and Tumor Growth by the RUNX1 Transcription Factor. Mol Cancer Res. 2018 Dec;16(12):1952-1964. doi: 10.1158/1541-7786.MCR-18-0135. Epub 2018 Aug 6. PMID: 30082484; PMCID: PMC6289193.
Hong D, Fritz AJ, Zaidi SK, van Wijnen AJ, Nickerson JA, Imbalzano AN, Lian JB, Stein JL, Stein GS. Epithelial-to-mesenchymal transition and cancer stem cells contribute to breast cancer heterogeneity. J Cell Physiol. 2018 Dec;233(12):9136-9144. doi: 10.1002/jcp.26847. Epub 2018 Jul 3. PMID: 29968906; PMCID: PMC6185773.
VanOudenhove JJ, Grandy RA, Ghule PN, Lian JB, Stein JL, Zaidi SK, Stein GS. Unique Regulatory Mechanisms for the Human Embryonic Stem Cell Cycle. J Cell Physiol. 2017 Jun;232(6):1254-1257. doi: 10.1002/jcp.25567. Epub 2017 Jan 31. PMID: 27532275; PMCID: PMC5315681.
VanOudenhove JJ, Medina R, Ghule PN, Lian JB, Stein JL, Zaidi SK, Stein GS. Precocious Phenotypic Transcription-Factor Expression During Early Development. J Cell Biochem. 2017 May;118(5):953-958. doi: 10.1002/jcb.25723. Epub 2017 Jan 11. PMID: 27591551; PMCID: PMC5336526.